Microrna-320 Family is Downregulated in Colorectal Adenoma and Affects Tumor Proliferation by Targeting Cdk6

Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Seiichi Takahashi, Yoshitaka Kinouchi, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, nonneoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with amimic control or miRNA mimics were measured using qRTPCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured.RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenomaand submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression.CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

Original languageEnglish
Pages (from-to)532-542
Number of pages11
JournalWorld Journal of Gastrointestinal Oncology
Volume8
Issue number7
DOIs
Publication statusPublished - 2016 Jan 1

Keywords

  • CDK6
  • Colorectal adenoma
  • Colorectal cancer
  • Laterally spreading type
  • MiR-320 family

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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