LINC00839 promotes malignancy of liver cancer via binding FMNL2 under hypoxia.

Liver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.

Early outcomes of a rural-oriented physician education programme against rural physician shortages in Guangxi province: a prospective cohort study.

OBJECTIVES: This study aimed to investigate early outcomes of one of the first medical undergraduate education programmes with a goal of mitigating severe rural physician shortages in China, which was developed by Guangxi Medical University (GXMU) and was called the Rural-oriented Free Tuition Medical Education (RTME)-GXMU programme. DESIGN: A prospective cohort study comprising a baseline investigation and follow-up research was conducted to dynamically observe the evolution of the RTME-GXMU programme that began since 2010. PARTICIPANTS: 380 RTME-GXMU graduates and 383 non-RTME-GXMU graduates from GXMU who completed trainings between 2015 and 2018 were recruited in the baseline investigation. Among them, 285 RTME-GXMU and 283 non-RTME-GXMU graduates responded to the follow-up research. MAIN OUTCOME MEASURES: Graduate practice location, registered specialty, passing rate of the National Medical Licensing Examination (NMLE), specialty of residency programme and contract compliance for the RTME-GXMU graduates. RESULTS: By the end of 2018, 100% of the 2015 RTME-GXMU graduates enrolled in this study practised in rural township health centres and registered themselves as general practitioners (GPs). All the RTME-GXMU graduates had completed or were attending residency programmes of general practice (GP). The above data stood in stark contrast to that of the non-RTME-GXMU graduates among whom as few as 1.06% worked in rural areas, 2.13% registered as GPs and less than 3% chose GP residency programmes. No significant differences were detected on passing rates of the NMLE between the two groups. Only one RTME-GXMU graduate broke the contract and dropped off the programme. CONCLUSIONS: The RTME-GXMU programme has achieved encouraging early outcomes. Reduced entry score and proper usage of urban primary care institutions are two key approaches contributing to these positive early results.

IL-22 inactivates hepatic stellate cells via downregulation of the TGF-ß1/Notch signaling pathway.

Interleukin-22 (IL-22) inhibits liver fibrosis by inducing hepatic stellate cell (HSC) senescence, primarily through the activation of signal transducer and activator of transcription 3 signaling. However, whether other signaling pathways are involved remains unknown. The present study assessed the regulatory mechanism between IL­22 and the Notch signaling pathway in vitro. The results revealed that IL­22 had anti­proliferative effects on HSC­T6 cells, and cellular inactivation was reflected by simultaneous inhibition of α­smooth muscle actin, transforming growth factor-ß1 (TGF­ß1), tumor necrosis factor-α and intercellular adhesion molecule 1. Treatment with TGF­ß1 resulted in significant Notch3 upregulation and activation of its downstream effectors Hes family basic helix­loop­helix (bHLH) transcription factor (Hes)-1, Hes­5 and Hes related family BHLH transcription factor with YRPW motif 1. Furthermore, this effect was markedly reversed by further treatment with IL­22, indicating there may be regulatory cascades of IL­22/TGF­ß1/Notch signaling in HSC­T6 cells. The results of the present study demonstrated an inhibitory function of IL­22 towards Notch signaling in hepatic cells, providing evidence that Notch may serve as a novel target for liver fibrosis.