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RNA sequencing-based microRNA expression signature in esophageal squamous cell carcinoma: oncogenic targets by antitumor miR-143-5p and miR-143-3p regulation

Journal of Human Genetics volume 65, pages 1019–1034 (2020)Cite this article

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Abstract

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.

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Acknowledgements

This study was supported by KAKENHI grants (grant nos. 17H04285, 18K08626, 18K09338, 18K16322, and 19K09077).

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Authors and Affiliations

  1. Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan

    Masumi Wada, Takako Tanaka, Tetsuya Idichi, Masahiro Noda, Ken Sasaki, Yoshiaki Kita, Hiroshi Kurahara, Kosei Maemura & Shoji Natsugoe

  2. Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan

    Yusuke Goto, Reona Okada & Naohiko Seki

  3. Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan

    Shogo Moriya

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Wada, M., Goto, Y., Tanaka, T. et al. RNA sequencing-based microRNA expression signature in esophageal squamous cell carcinoma: oncogenic targets by antitumor miR-143-5p and miR-143-3p regulation. J Hum Genet 65, 1019–1034 (2020). https://doi.org/10.1038/s10038-020-0795-x

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