Wada Masumi, Goto Yusuke, Tanaka Takako, Okada Reona, Moriya Shogo, Idichi Tetsuya, Noda Masahiro, Sasaki Ken, Kita Yoshiaki, Kurahara Hiroshi, Maemura Kosei, Natsugoe Shoji, Seki Naohiko
Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan.
Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Hum Genet. 2020 Nov;65(11):1019-1034. doi: 10.1038/s10038-020-0795-x. Epub 2020 Jul 4.
Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs were candidates for antitumor miRNAs in ESCC cells. Analysis of the signature revealed that several passenger strands of miRNAs were significantly downregulated in ESCC, e.g., miR-28-3p, miR-30a-3p, miR-30c-3p, miR-133a-3p, miR-139-3p, miR-143-5p, and miR-145-3p. Recent studies indicate that some passenger strands of miRNAs closely involved in cancer pathogenesis. In this study, we focused on both strands of pre-miR-143, and investigated their antitumor roles and target oncogenes in ESCC. Ectopic expression of miR-143-5p and miR-143-3p significantly attenuated malignant phenotypes (e.g., proliferation, migration, and invasive abilities) in ESCC cell lines. We revealed that six genes (HN1, HMGA2, NETO2, STMN1, TCF3, and MET) were putative targets of miR-143-5p regulation, and one gene (KRT80) was a putative target of miR-143-3p regulation in ESCC cells. Our ESCC miRNA signature and analysis strategy provided important insights into the molecular pathogenesis of ESCC.
异常表达的微小RNA（miRNA）破坏细胞内RNA网络，并促进癌细胞的恶性转化。利用最新的RNA测序技术，我们新创建了食管鳞状细胞癌（ESCC）的miRNA表达特征。共有47种miRNA在ESCC组织中下调，这些miRNA是ESCC细胞中抗肿瘤miRNA的候选者。对该特征的分析表明，几种miRNA的过客链在ESCC中显著下调，例如miR-28-3p、miR-30a-3p、miR-30c-3p、miR-133a-3p、miR-139-3p、miR-143-5p和miR-145-3p。最近的研究表明，一些miRNA的过客链与癌症发病机制密切相关。在本研究中，我们聚焦于pre-miR-143的两条链，并研究了它们在ESCC中的抗肿瘤作用和靶癌基因。miR-143-5p和miR-143-3p的异位表达显著减弱了ESCC细胞系中的恶性表型（如增殖、迁移和侵袭能力）。我们发现六个基因（HN1、HMGA2、NETO2、STMN1、TCF3和MET）是ESCC细胞中miR-143-5p调控的假定靶标，一个基因（KRT80）是miR-143-3p调控的假定靶标。我们的ESCC miRNA特征和分析策略为ESCC的分子发病机制提供了重要见解。
