CASC15 promotes epithelial to mesenchymal transition and facilitates malignancy of hepatocellular carcinoma cells by increasing TWIST1 gene expression via miR-33a-5p sponging
Authors: Yanju Yan
Gongbin Chen
Qingxia Fan
Yang Li
Journal: European journal of pharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: CASC15; Epithelial-to-mesenchymal transition; Hepatocellular carcinoma; TWIST1.
Affiliations: Department One of Oncology, Shangqiu First People's Hospital, Shangqiu, 476100, Henan, China., Department One of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. Electronic address: .

Abstract:  Long noncoding RNA cancer susceptibility candidate 15 (CASC15) facilitates progression of hepatocellular carcinoma (HCC) cells, but the molecular mechanisms remain unknown. CASC15 co-expressing genes were explored in the Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset. Putative co-expressing genes were analyzed by Gene Ontology and biological pathway enrichment analysis. CASC15 overexpression or knockdown and TWIST1 overexpression or knockdown in HCC cells was achieved by lentiviral transduction or plasmid transfection. Interaction between CASC15 and microRNA-33a-5p (miR-33a-5p) was verified by argonaute 2-RNA Immunoprecipitation (AGO2-RIP) and luciferase reporter assays. HCC cell malignancy was determined by cell proliferation, apoptosis, migration and invasion assays. Tumorigenicity was evaluated by xenograft assay. Epithelial-to-mesenchymal transition (EMT) of HCC cells was assessed by Western blot. TWIST1, sex-determining region Y-related high-mobility group box 4 (Sox4) and Versican were found as putative CASC15 co-expressing genes. CASC15 positively regulated TWIST1 gene expression as well as protein level of Sox4 and Versican in HCC cells. Positive correlation in expression between CASC15 and TWIST1 mRNA was verified in 42 pairs of HCC pathologic and adjacent tissue specimens. CASC15 upregulated TWIST1 gene expression in HCC cells by sponging miR-33a-5p. CASC15 promoted EMT in HCC cells by increasing N-cadherin and Vimentin protein level while decreasing that of E-cadherin through TWIST1. CASC15 facilitated HCC cell proliferation, migration and invasion while reducing cell apoptosis through TWIST1. CASC15 facilitated the tumorigenicity of HCC cells in vivo. a CASC15 could promote EMT and facilitate malignancy of HCC cells by increasing TWIST1 gene expression via miR-33a-5p sponging. 

Retracted: No

PubPeer comments:
 Most Western blots in this paper appear to have the same background, similar to the 400+ papers that might belong to the same paper mill, as discussed in these blog posts: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) These blots might show a different background pattern, but it is striking how the same background is visible in most of the different immunoblots. Here is Figure 5I (images made darker to bring out the background): ![file] Figure 6I: ![file] Figure 9G H (some features marked with boxes of the same color): ![file] , 
 Figure 6J. * Blue boxes: Two panels appear to look very similar * The distribution of events over the different quadrants does not appear to look as expected for flow cytometry images ![file] ,