Micro RNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

• 作者: 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
• 来源期刊: 世界胃肠肿瘤学杂志：英文版（电子版）
• 学科: 医学
• 关键词: CDK6 COLORECTAL cancer Mi R-320 FAMILY COLORECTAL ADENOMA Laterally SPREADING type
• 年，卷（期）: 2016,（7）
• 页码范围: 532-542
• 页数: 11页
• 分类号: R735.34

摘要

AIM: To investigate the microR NA(miR NA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miR NA 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 miR NA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miR NA mimics. mR NA and protein levels of the target gene in colon cancer cell lines with a mimic control or miR NA mimics were measured using qR TPCR and Western blotting. The expression levels of miR NA and target gene in colorectal tissue samples were also measured.RESULTS: Microarray analysis identified that the miR-320 family, including miR-320 a, miR-320 b, miR-320 c, miR-320 d and miR-320 e, were differentially expressed in adenomaand submucosal invasive carcinoma. The mi R-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 mR NA 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.