LncRNA HOTAIR suppresses cell apoptosis, autophagy and induces cell proliferation in cholangiocarcinoma by modulating the miR-204-5p/HMGB1 axis.

Cholangiocarcinoma (CCA) is a malignant tumor in the world. LncRNA HOX transcript antisense intergenic RNA (HOTAIR) was identified as a crucial regulator in various cancers including CCA. This study aimed to unravel the functions of HOTAIR and its biological mechanism in CCA, hinting for the new therapeutic targets in CCA. The levels of HOTAIR, miR-204-5p and HMGB1 in CCA tissues and cell lines (HuB28 and HuCCT1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted to detect the protein levels of LC3-I, LC3-II, Beclin-1 and HMGB1. The relationships among HOTAIR, miR-204-5p and HMGB1 were examined by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay. Cell proliferation ability and apoptosis rate were assessed by CCK8 assay and flow cytometry, respectively. in vivo experiment was conducted to examine the bio-functions of HOTAIR in nude mice. HOTAIR and HMGB1 were over-expressed, while miR-204-5p was lowly expressed in CCA tissues and cells. The dual-luciferase reporter assay indicated that miR-204-5p was a target of HOTAIR, and HMGB1 was a target of miR-204-5p. The restoration experiments showed that HOTAIR repressed cell apoptosis, autophagy and promoted cell proliferation via miR-204-5p/HMGB1 axis. Additionally, HOTAIR silencing retarded the xenograft tumor growth by up-regulation of miR-204-5p and down-regulation of HMGB1. These data unraveled that lncRNA HOTAIR regulated HMGB1 to suppress cell apoptosis, autophagy and induce cell proliferation by sponging miR-204-5p in CCA. Thus, this new regulatory pathway may provide new therapeutic targets for CCA.

Lu M ，Qin X ，Zhou Y ，Li G ，Liu Z ，Yue H ，Geng X ... -  《-》

LncRNA DANCR affected cell growth, EMT and angiogenesis by sponging miR-345-5p through modulating Twist1 in cholangiocarcinoma.

Zhu CY ，Fan CR ，Zhang YL ，Sun QX ，Yan MJ ，Wei W ，Liu GF ，Liu JJ ... -  《-》

Long non-coding RNA MEG3 represses cholangiocarcinoma by regulating miR-361-5p/TRAF3 axis.

Lu WX 《-》

lncRNA SNHG16 Mediates Cell Proliferation and Apoptosis in Cholangiocarcinoma by Directly Targeting miR-146a-5p/GATA6 Axis.

Cholangiocarcinoma (CCA) is a malignant tumour with high recurrence and mortality rates and poor prognosis. However, the pathogenic mechanism remains unclear. In the present study, we aimed to investigate the roles and regulatory mechanism of SNHG16 in the occurrence and development of CCA. Gene Expression Profiling Interactive Analysis (GEPIA) was used to predict the expressions of SNHG16 and GATA6 in CCA samples from TCGA database. The levels of SNHG16, miR-146a-5p and GATA6 were evaluated using qRT-PCR. CCK-8 and flow cytometry assays were conducted to evaluate cell proliferation and apoptosis, respectively. Western blotting was applied to analyse the protein levels of GATA6 and apoptosis-related proteins. SNHG16 was significantly elevated in CCA tissues from TCGA database and CCA cell lines. Moreover, downregulation of SNHG16 restricted cell proliferation and increased apoptotic rate of RBE and HuCCT1 cells. miR-146a-5p, a downstream target of SNHG16, was shown to be an intermediate mediator of GATA6 expression regulated by SNHG16. In addition, either the miR-146a-5p inhibitor or overexpression of GATA6 obviously impaired the regulatory effects of SNHG16 downregulation in RBE and HuCCT1 cells. These data demonstrated that SNHG16 promoted cell proliferation and repressed apoptosis by regulating the miR-146a-5p/GATA6 axis, which provides some helpful insights for the diagnosis and treatment of CCA.

Wu T ，Lei MS ，Gao XZ ，Xiong TG ，Yang K ，Gong Q ，Tang R ，Tian YP ，Fu XH ... -  《-》

Up-regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR-296-5p.

LncRNAs has been demonstrated to modulate neoplastic development by modulating downstream miRNAs and functional genes. In this study, we aimed to detect the interaction among lncRNA ZFAS1 miR-296-5p and USF1. We explored the proliferation, migration and invasion of cholangiocarcinoma. The differentially expressed ZFAS1 was discovered in both tissues and cell lines by qRT-PCR. The targeting relationship between miR-296-5p and ZFAS1 or USF1 was validated by dual-luciferase assay. The impact of ZFAS1 on CCA cell proliferation was observed by CCK-8 assay. The protein expression of USF1 was determined by Western blot. The effects of ZFAS1, miR-296-5p and USF1 on tumour growth were further confirmed using xenograft model. LncRNA ZFAS1 expression was relatively up-regulated in tumour tissues and cells while miR-296-5p was significantly down-regulated. Knockdown of ZFAS1 significantly suppressed tumour proliferation, migration, invasion and USF1 expression. Overexpressed miR-296-5p suppressed cell proliferation and metastasis. Knockdown of USF1 inhibited cell proliferation and metastasis and xenograft tumour growth. In conclusion, ZFAS1 might promote cholangiocarcinoma proliferation and metastasis by modulating USF1 via miR-296-5p.

Li Z ，Jiang X ，Huang L ，Li J ，Ji D ，Xu Y ，Leng K ，Cui Y ... -  《-》