Ministry of Health

Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

Circular RNAs, a novel class of endogenous noncoding RNAs, are characterized by their covalently closed loop structures without a 5' cap or a 3' Poly A tail. Although the mechanisms of circular RNAs' generation and function are not fully clear, recent research has shown that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours. This review summarizes some information about categories, biogenesis, functions at the molecular level, properties of circular RNAs and the possibility of circular RNAs as biomarkers in cancers.

Despite dramatic improvements in survival, nutrition, and education over recent decades, today's children face an uncertain future. Climate change, ecological degradation, migrating populations, conflict, pervasive inequalities, and predatory commercial practices threaten the health and future of children in every country. In 2015, the world's countries agreed on the Sustainable Development Goals (SDGs), yet nearly 5 years later, few countries have recorded much progress towards achieving them. This Commission presents the case for placing children, aged 0-18 years, at the centre of the SDGs: at the heart of the concept of sustainability and our shared human endeavour. Governments must harness coalitions across sectors to overcome ecological and commercial pressures to ensure children receive their rights and entitlements now and a liveable planet in the years to come.

In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.

Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. METHODS: We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. RESULTS: Among the PPD-positive subjects, the incidence of tuberculosis in the three groups that received preventive therapy was lower than the rate in the placebo group (P=0.002 by the log-rank test). The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08). Among the subjects with anergy, the relative risk of tuberculosis was 0.83 (95 percent confidence interval, 0.34 to 2.04) with isoniazid as compared with placebo. Side effects were more common with the multidrug regimens, and particularly with the regimen containing pyrazinamide. Survival did not differ among the groups, but the subjects with anergy had a higher mortality rate than the PPD-positive subjects. CONCLUSIONS: A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults. Multidrug regimens with isoniazid and rifampin taken for three months also reduce the risk of tuberculosis.

<b>Objectives</b>&nbsp;To estimate small for gestational age birth prevalence and attributable neonatal mortality in low and middle income countries with the INTERGROWTH-21^st birth weight standard. <b>Design</b>&nbsp;Secondary analysis of data from the Child Health Epidemiology Reference Group (CHERG), including 14 birth cohorts with gestational age, birth weight, and neonatal follow-up.&nbsp;Small for gestational age was defined as infants weighing less than the 10th centile birth weight for gestational age and sex with the multiethnic, INTERGROWTH-21^st birth weight standard.&nbsp;Prevalence of small for gestational age and neonatal mortality risk ratios were calculated and pooled among these datasets at the regional level.&nbsp;With available national level data, prevalence of small for gestational age and population attributable fractions of neonatal mortality attributable to small for gestational age were estimated. <b>Setting</b>&nbsp;CHERG birth cohorts from 14 population based sites in low and middle income countries. <b>Main outcome measures</b>&nbsp;In low and middle income countries in the year 2012, the number and proportion of infants born small for gestational age; number and proportion of neonatal deaths attributable to small for gestational age; the number and proportion of neonatal deaths that could be prevented by reducing the prevalence of small for gestational age to 10%. <b>Results</b>&nbsp;In 2012, an estimated 23.3 million infants (uncertainty range 17.6 to 31.9; 19.3% of live births) were born small for gestational age in low and middle income countries. Among these, 11.2 million (0.8 to 15.8) were term and not low birth weight (≥2500 g), 10.7 million (7.6 to 15.0) were term and low birth weight (&lt;2500 g) and 1.5 million (0.9 to 2.6) were preterm. In low and middle income countries, an estimated 606 500 (495 000 to 773 000) neonatal deaths were attributable to infants born small for gestational age, 21.9% of all neonatal deaths. The largest burden was in South Asia, where the prevalence was the highest (34%); about 26% of neonatal deaths were attributable to infants born small for gestational age. Reduction of the prevalence of small for gestational age from 19.3% to 10.0% in these countries could reduce neonatal deaths by 9.2% (254 600 neonatal deaths; 164 800 to 449 700). <b>Conclusions</b>&nbsp;In low and middle income countries, about one in five infants are born small for gestational age, and one in four neonatal deaths are among such infants. Increased efforts are required to improve the quality of care for and survival of these high risk infants in low and middle income countries

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.

Schistosomiasis remains one of the most prevalent parasitic diseases in developing countries. After malaria, schistosomiasis is the most important tropical disease in terms of human morbidity with significant economic and public health consequences. Although schistosomiasis has recently attracted increased focus and funding for control, it has been estimated that less than 20% of the funding needed to control the disease in Africa is currently available. In this article the following issues are discussed: the rationale, development and objectives of the Schistosomiasis Control Initiative (SCI)-supported programmes; the management approaches followed to achieve implementation by each country; mapping, monitoring and evaluation activities with quantifiable impact of control programmes; monitoring for any potential drug resistance; and finally exit strategies within each country. The results have demonstrated that morbidity due to schistosomiasis has been reduced by the control programmes. While challenges remain, the case for the control of schistosomiasis has been strengthened by research by SCI teams and the principle that a national programme using 'preventive chemotherapy' can be successfully implemented in sub-Saharan Africa, whenever the resources are available. SCI and partners are now actively striving to raise further funds to expand the coverage of integrated control of neglected tropical diseases (NTDs) in sub-Saharan Africa.

Despite considerable efforts, malaria is still one of the most devastating infectious diseases in the tropics. The rapid spread of antimalarial drug resistance currently compounds this grim picture. In this paper, we review the history of antimalarial drug resistance and the methods for monitoring it and assess the current magnitude and burden of parasite resistance to two commonly used drugs: chloroquine and sulfadoxine-pyrimethamine. Furthermore, we review the factors involved in the emergence and spread of drug resistance and highlight its public health importance. Finally, we discuss ways of dealing with such a problem by using combination therapy and suggest some of the research themes needing urgent answers.

Knowledge of the baseline malaria transmission in a given environment is important to guide malaria control interventions. However, in Uganda, recent information on malaria transmission intensity is lacking. Therefore, a 1-year entomological study was conducted in seven ecologically different sites throughout the country to assess spatial and temporal patterns in malaria transmission intensity. Anopheles gambiae sensu stricto was the main vector in five of the seven study sites, and An. funestus was the most important vector in the two other sites. In a peri-urban village, An. arabiensis contributed substantially to malaria transmission. Clear differences in annual entomological inoculation rates (AEIR) were observed between the study sites, ranging from 4 infective bites per person per year in the southwestern part of the country to >1,500 infective bites per person per year in a swampy area near the Nile River. Between villages with parasite prevalences of >or= 80% in children between 1 and 9 years old, a 4-fold difference in AEIR was observed. Based on the observed behavior of the vectors, insecticide-treated bed nets will be highly effective in controlling malaria. However, in the high transmission areas, additional measures will be needed to reduce the malaria burden to acceptable levels.

An outbreak of Ebola disease was reported from Gulu district, Uganda, on 8 October 2000. The outbreak was characterized by fever and haemorrhagic manifestations, and affected health workers and the general population of Rwot-Obillo, a village 14 km north of Gulu town. Later, the outbreak spread to other parts of the country including Mbarara and Masindi districts. Response measures included surveillance, community mobilization, case and logistics management. Three coordination committees were formed: National Task Force (NTF), a District Task Force (DTF) and an Interministerial Task Force (IMTF). The NTF and DTF were responsible for coordination and follow-up of implementation of activities at the national and district levels, respectively, while the IMTF provided political direction and handled sensitive issues related to stigma, trade, tourism and international relations. The international response was coordinated by the World Health Organization (WHO) under the umbrella organization of the Global Outbreak and Alert Response Network. A WHO/CDC case definition for Ebola was adapted and used to capture four categories of cases, namely, the 'alert', 'suspected', 'probable' and 'confirmed cases'. Guidelines for identification and management of cases were developed and disseminated to all persons responsible for surveillance, case management, contact tracing and Information Education Communication (IEC). For the duration of the epidemic that lasted up to 16 January 2001, a total of 425 cases with 224 deaths were reported countrywide. The case fatality rate was 53%. The attack rate (AR) was highest in women. The average AR for Gulu district was 12.6 cases/10 000 inhabitants when the contacts of all cases were considered and was 4.5 cases/10 000 if limited only to contacts of laboratory confirmed cases. The secondary AR was 2.5% when nearly 5000 contacts were followed up for 21 days. Uganda was finally declared Ebola free on 27 February 2001, 42 days after the last case was reported. The Government's role in coordination of both local and international support was vital. The NTF and the corresponding district committees harmonized implementation of a mutually agreed programme. Community mobilization using community-based resource persons and political organs, such as Members of Parliament was effective in getting information to the public. This was critical in controlling the epidemic. Past experience in epidemic management has shown that in the absence of regular provision of information to the public, there are bound to be deleterious rumours. Consequently rumour was managed by frank and open discussion of the epidemic, providing daily updates, fact sheets and press releases. Information was regularly disseminated to communities through mass media and press conferences. Thus all levels of the community spontaneously demonstrated solidarity and response to public health interventions. Even in areas of relative insecurity, rebel abductions diminished considerably.

BACKGROUND: Untimely, incomplete and inaccurate data are common challenges in planning, monitoring and evaluation of health sector performance, and health service delivery in many sub-Saharan African settings. We document Uganda's experience in strengthening routine health data reporting through the roll-out of the District Health Management Information Software System version 2 (DHIS2). METHODS: DHIS2 was adopted at the national level in January 2011. The system was initially piloted in 4 districts, before it was rolled out to all the 112 districts by July 2012. As part of the roll-out process, 35 training workshops targeting 972 users were conducted throughout the country. Those trained included Records Assistants (168, 17.3%), District Health Officers (112, 11.5%), Health Management Information System Focal Persons (HMIS-FPs) (112, 11.5%), District Biostatisticians (107, 11%) and other health workers (473, 48.7%). To assess improvements in health reporting, we compared data on completeness and timeliness of outpatient and inpatient reporting for the period before (2011/12) and after (2012/13) the introduction of DHIS2. We reviewed data on the reporting of selected health service coverage indicators as a proxy for improved health reporting, and documented implementation challenges and lessons learned during the DHIS2 roll-out process. RESULTS: Completeness of outpatient reporting increased from 36.3% in 2011/12 to 85.3% in 2012/13 while timeliness of outpatient reporting increased from 22.4% to 77.6%. Similarly, completeness of inpatient reporting increased from 20.6% to 57.9% while timeliness of inpatient reporting increased from 22.5% to 75.6%. There was increased reporting on selected health coverage indicators (e.g. the reporting of one-year old children who were immunized with three doses of pentavelent vaccine increased from 57% in 2011/12 to 87% in 2012/13). Implementation challenges included limited access to computers and internet (34%), inadequate technical support (23%) and limited worker force (18%). CONCLUSION: Implementation of DHIS2 resulted in improved timeliness and completeness in reporting of routine outpatient, inpatient and health service usage data from the district to the national level. Continued onsite support supervision and mentorship and additional system/infrastructure enhancements, including internet connectivity, are needed to further enhance the performance of DHIS2.

As highland regions of Africa historically have been considered free of malaria, recent epidemics in these areas have raised concerns that high elevation malaria transmission may be increasing. Hypotheses about the reasons for this include changes in climate, land use and demographic patterns. We investigated the effect of land use change on malaria transmission in the south-western highlands of Uganda. From December 1997 to July 1998, we compared mosquito density, biting rates, sporozoite rates and entomological inoculation rates between 8 villages located along natural papyrus swamps and 8 villages located along swamps that have been drained and cultivated. Since vegetation changes affect evapotranspiration patterns and, thus, local climate, we also investigated differences in temperature, humidity and saturation deficit between natural and cultivated swamps. We found that on average all malaria indices were higher near cultivated swamps, although differences between cultivated and natural swamps were not statistically significant. However, maximum and minimum temperature were significantly higher in communities bordering cultivated swamps. In multivariate analysis using a generalized estimating equation approach to Poisson regression, the average minimum temperature of a village was significantly associated with the number of Anopheles gambiae s.l. per house after adjustment for potential confounding variables. It appears that replacement of natural swamp vegetation with agricultural crops has led to increased temperatures, which may be responsible for elevated malaria transmission risk in cultivated areas.

BACKGROUND: Current malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too complex for field deployment. A new commercial molecular assay based on loop-mediated isothermal amplification (LAMP) was assessed for field use. METHODS: Malaria LAMP (Eiken Chemical, Japan) was evaluated for samples from 272 outpatients at a rural Ugandan clinic and compared with expert microscopy, nested PCR, and quantitative PCR (qPCR). Two technicians performed the assay after 3 days of training, using 2 alternative blood sample-preparation methods and visual interpretation of results by fluorescence assay. RESULTS: Compared with 3-well nested PCR, the sensitivity of both LAMP and single-well nested PCR was 90%; the microscopy sensitivity was 51%. For samples with a Plasmodium falciparum qPCR titer of ≥ 2 parasites/µL, LAMP sensitivity was 97.8% (95% confidence interval, 93.7%-99.5%). Most false-negative LAMP results involved samples with parasitemia levels detectable by 3-well nested PCR but very low or undetectable by qPCR. CONCLUSIONS: Malaria LAMP in a remote Ugandan clinic achieved sensitivity similar to that of single-well nested PCR in a United Kingdom reference laboratory. LAMP dramatically lowers the detection threshold achievable in malaria-endemic settings, providing a new tool for diagnosis, surveillance, and screening in elimination strategies.

Technical guidelines for the control of Ebola hemorrhagic fever (EHF) indicate that understanding local views and responses to an outbreak is essential. However, few studies with such information exist. Thus, we used qualitative and quantitative methods to determine how local residents of Gulu, Uganda, viewed and responded to the 2000–2001 outbreak of EHF. Results indicated that Acholi people used at least three explanatory models to explain and respond to the outbreak; indigenous epidemic control measures were often implemented and consistent with those being promoted by healthcare workers; and some cultural practices amplified the outbreak (e.g., burial practices). However, most persons were willing to modify and work with national and international healthcare workers.

Immunological and clinical profiles were evaluated in 2 groups: human immunodeficiency virus (HIV)-uninfected and HIV-infected patients, with newly diagnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive healthy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy. At the time of diagnosis, purified protein derivative (PPD)-stimulated production of interferon (IFN)-gamma by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transforming growth factor (TGF)-beta and interleukin (IL)-10 were increased. In longitudinal studies, PPD stimulated production of IL-10 and TGF-beta returned to baseline by 3 months, whereas IFN-gamma production remained depressed for at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.

OBJECTIVE: To monitor the HIV-1 epidemic in Western Uganda and the possible impact of interventions. DESIGN: Results from sentinel surveillance of HIV-1 seroprevalence were compared with cross-sectional serosurvey data and model simulations. METHODS: Age-specific trends in HIV-1 prevalence between 1991 and 1997 amongst antenatal clinic (ANC) attenders in the town of Fort Portal, where a comprehensive AIDS control programme has been implemented since 1991, were analysed. Results were compared with outputs from a mathematical model simulating the HIV-1 epidemic in Uganda. Two scenarios were modelled: one without and one with behaviour change. Sentinel surveillance data were compared with data from a population-based HIV-1 serosurvey at the study site, which was carried out in early 1995. RESULTS: Data from 3271 ANC attenders identified greater education and being single as risk factors for HIV-1 infection. A significant decrease of risk for women with secondary school education over time was observed, whereas the risk for illiterate women remained high. Among women aged 15-19 years (n = 1045) education and marital status-adjusted HIV-1 prevalence declined steadily from 32.2% in 1991 to 10.3% in 1997. For 20-24-year-old women (n = 1010) HIV-1 prevalence increased until 1993 from 19.9% to 31.7% and decreased thereafter (21.7% in 1997). These trends closely follow the prediction of the model simulation assuming behaviour change, and for 1995-1997, confidence intervals of the HIV-1 prevalence estimate exclude the model output for an uninfluenced epidemic. No clear trends of HIV-1 prevalence were found in older women (n = 1216) and comparisons with the model were ambiguous. Sentinel surveillance data at the time of the population survey closely reflected results for the female general population sample for the two younger age-groups (15-19 and 20-24 years). In contrast, pregnant women aged 25-29 years showed significantly lower rates than the population sample (20.8% versus 45.1%). CONCLUSION: HIV-1 prevalence amongst ANC attenders aged 15-24 years can be used to monitor the HIV-1 epidemic in the given setting. Declining trends of HIV-1 prevalence in women aged 15-19 and 20-24 years most likely correspond to a reduced HIV-1 incidence attributable to changes in behaviour. Our data also show that sentinel surveillance data need to be age-stratified to give useful information.

Despite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression. We conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. The study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (ORadj = 5.3, 95%CI = 4.6–6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9–3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression. Young age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

// Hao Bo 1,2,3 , Zhaojian Gong 2,4 , Wenling Zhang 2 , Xiayu Li 3 , Yong Zeng 1 , Qianjin Liao 1 , Pan Chen 1 , Lei Shi 4 , Yu Lian 2 , Yizhou Jing 2 , Ke Tang 2 , Zheng Li 1,2,3 , Yanhong Zhou 1,2,3 , Ming Zhou 1,2,3 , Bo Xiang 1,2,3 , Xiaoling Li 1,2,3 , Jianbo Yang 1,5 , Wei Xiong 1,2,3 , Guiyuan Li 1,2,3 and Zhaoyang Zeng 1,2,3 1 Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China 2 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China 3 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 4 Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China 5 Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America Correspondence to: Zhaoyang Zeng, email: // Keywords : long non-coding RNA (LncRNA); AFAP1 antisense RNA1 (AFAP1-AS1); nasopharyngeal carcinoma (NPC); metastasis; prognosis Received : March 10, 2015 Accepted : April 22, 2015 Published : May 09, 2015 Abstract Altered expression of long noncoding RNAs (lncRNAs) associated with human carcinogenesis. We performed a cDNA microarray analysis of lncRNA expression in 12 cases of nasopharyngeal carcinoma (NPC) and 4 non-tumor nasopharyngeal epitheliums. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was identified and selected for further study. AFAP1-AS1 expression was upregulated in NPC and associated with NPC metastasis and poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the NPC cell migration and invasive capability. AFAP1-AS1 knockdown also increased AFAP1 protein expression. Proteomic and bioinformatics analyses suggested that AFAP1-AS1 affected the expression of several small GTPase family members and molecules in the actin cytokeratin signaling pathway. AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. AFAP1-AS1 might be a potential novel marker that can predict cancer patient prognosis and as a potential therapeutic target for NPC.