H19, a Long Non-coding RNA, Mediates Transcription Factors and Target Genes through Interference of MicroRNAs in Pan-Cancer
MOLECULAR THERAPY-NUCLEIC ACIDS
Authors: Li, Aimin; Mallik, Saurav; Luo, Haidan; Jia, Peilin; Lee, Dung-Fang; Zhao, Zhongming
Abstract
Long non-coding RNAs (lncRNAs) have recently been found to be important in gene regulation. lncRNA H19 has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. In this study, we developed a novel analytic approach by integrating the synergistic regulation among lncRNAs (e.g., H19), transcription factors (TFs), target genes, and microRNAs (miRNAs) and then applied it to the pan-cancer expression datasets from The Cancer Genome Atlas (TCGA). Using linear regression models, we identified 88 H19-TF-gene co-regulatory triplets, in which 93% of the TF-gene pairs were related to cancer, indicating that our approach was effective to identify disease-related lncRNA-TF-gene co-regulation mechanisms. lncRNAs can function as miRNA sponges. Our further experiments found that H19 might regulate SP1-TGFBR2 through let-7b and miR-200b, ETS1-TGFBR2 through miR-29a and miR-200b, and STAT3-KLF11 through miR-17 in breast cancer cell lines. Our work suggests that miRNA-mediated lncRNA-TF-gene co-regulation is complicated yet important in cancer.
MiR-193a-5p and-3p Play a Distinct Role in Gastric Cancer: miR-193a-3p Suppresses Gastric Cancer Cell Growth by Targeting ETS1 and CCND1
ANTICANCER RESEARCH
Authors: Chou, Nan-Hua; Lo, Yi-Hao; Wang, Kuo-Chiang; Kang, Chi-Hsiang; Tsai, Chung-Yu; Tsai, Kuo-Wang
Abstract
Background/Aim: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. Materials and Methods: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. Results: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. Conclusion: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression.