Full length articleCASC15 promotes epithelial to mesenchymal transition and facilitates malignancy of hepatocellular carcinoma cells by increasing TWIST1 gene expression via miR-33a-5p sponging
Section snippets
Introductions
As the most frequently diagnosed primary liver cancer, hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related death (Forner et al., 2018; Llovet et al., 2016). Although the molecular mechanisms underlying HCC pathogenesis and progression are not fully under stood, non-coding RNAs such as microRNAs (miRNAs) and long noncoding RNAs (lncRNA) have been recognized as important regulators involved in these processes (Klingenberg et al., 2017; Wong et al., 2018).
LncRNA
Bioinformatic analysis
Transcriptome sequencing data in the Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma dataset was accessed through www.cbioportal.org/study?id=lihc_tcga#summary (Cerami et al., 2012). Data of 429 HCC samples were subject to the analysis. Expression of CASC15 was found positively correlated with that of a total of 477 genes with Spearman's rho >0.45, among which 455 were annotated in FunRich database. These putative CASC15 co-expressing genes in HCC were further analyzed by Gene
Bioinformatic analysis on putative CASC15 co-expressing genes in HCC
LncRNAs have been demonstrated to regulate tumor development through various of mechanisms, including functioning as so-called “competitive endogenous RNAs (ceRNAs)” that interact with miRNAs and inhibit their gene-silencing functions, thus liberating the expression of miRNA target genes. We first explored genes whose expression positively correlated with that of CASC15 in TCGA liver hepatocellular carcinoma data using Cbioportal online platform. Top 15 genes with highest or lowest Spearman's
Discussions
In the present research, we investigated the molecular mechanism underlying the tumor-promoting role of CASC15 in HCC. We first explored potential CASC15 co-expressing genes in TCGA Liver Hepatocellular Carcinoma dataset to see if CASC15 expression was positively correlated with that of any oncogene or tumor promoting gene in HCC. Sox4 and Versican were two of the 10 genes with highest Spearman's rho we found. Although we later chose TWIST1 for functional study, we propose that the possibility
Author agreement
All the author agree and approve the final manuscript.
Conflicts of interest
The co-authors declare that there are no financial and/or non-financial conflicts of interest existing in this research.
Funding
None.
Acknowledgements
Not applicable.
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2021, Biomedicine and PharmacotherapyCitation Excerpt :Although the interactions between CASC15 and target miRNAs or/and interlinking signalling pathways are complex in malignancy, the mechanism of action of CASC15 in tumorigenesis is mutual in a number of cancers. For example, miR-33a-5p was recognized as a target of CASC15 in liver cancer [19], gastric cancer [25], and TSCC [29]. In addition, CASC15 has been shown to regulate the Wnt/β-catenin signalling pathway in liver cancer [17] and colon cancer [27].
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2020, Chemico-Biological InteractionsCitation Excerpt :Twist1, a member of zinc-finger transcription factor, is the most important adjustment factor of EMT [41]. Many studies have shown that Twist1 inhibits E-cadherin transcription through binding to the E-box site in the E-cadherin promoter [42,43]. In addition, Twist1 not only promotes the EMT process, but also enhances drug resistance [44].