title: MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6.
abstract: OBJECTIVE
  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, non-neoplastic 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 a mimic control or miRNA mimics were measured using qRT-PCR 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 adenoma and 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.
  
  
  CONCLUSIONS
  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.
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Toshihiro
authors: T
authors: Tadano
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Yoichi
authors: Y
authors: Kakuta
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Shin
authors: S
authors: Hamada
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Yosuke
authors: Y
authors: Shimodaira
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Masatake
authors: M
authors: Kuroha
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Yoko
authors: Y
authors: Kawakami
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Tomoya
authors: T
authors: Kimura
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Hisashi
authors: H
authors: Shiga
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Katsuya
authors: K
authors: Endo
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Atsushi
authors: A
authors: Masamune
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Seiichi
authors: S
authors: Takahashi
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Yoshitaka
authors: Y
authors: Kinouchi
authors: Toshihiro Tadano, Yoichi Kakuta, Shin Hamada, Yosuke Shimodaira, Masatake Kuroha, Yoko Kawakami, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Atsushi Masamune, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors: Tooru
authors: T
authors: Shimosegawa
keywords: CDK6; Colorectal adenoma; Colorectal cancer; Laterally spreading type; MiR-320 family