title: Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer.
abstract: Colorectal cancer (CRC) has a high prevalence and mortality rate. Biomarkers for predicting the recurrence of CRC are not clinically available. This study investigated the role of circulating miR-15b in the prediction of CRC recurrence and the associated mechanism. miR-15b levels in plasma and tissues were measured by real-time PCR. Metastasis suppressor-1 (MTSS1) and Klotho protein expression were detected by Western blot and immunohistochemistry. Invasion and migration of CRC tumor cells were measured by transwell plates. Liver metastasis was established by intraspleen injection of HCT116 cells. Plasma miR-15b levels were significantly higher in CRC patients than in healthy controls, in CRC patients with metastasis than in CRC patients without metastasis, and in CRC patients with recurrence than in CRC patients without recurrence in the 5-year follow-up. miR-15b level in CRC tumors was significantly higher than that in peritumoral tissues. High plasma miR-15b level and negative MTSS1 and Klotho expression in tumor tissues significantly correlated with poor survival. Inhibition of miR-15b activity by adenovirus carrying antimiR-15b sequence significantly increased MTSS1 and Klotho protein expression and subsequently decreased colony formation ability, invasion, and migration of HCT116 cells in vitro and liver metastasis of HCT116 tumors in vivo. In conclusion, high abundance of circulating miR-15b correlated with tumor metastasis, recurrence, and poor patient prognosis through downregulation of MTSS1 and Klotho protein expression.
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China. chenyx008@yahoo.com.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road110, Changsha, Hunan, 410078, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, School of Basic Medical Science, Central South University, Xiangya Road110, Changsha, Hunan, 410078, People's Republic of China. rencaiping@csu.edu.cn.
authors.forename: Caiping
authors.initials: C
authors.lastname: Ren
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005966:Glucuronidase / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D000090265:Klotho Proteins; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C505361:MIRN15 microRNA, human; C486778:MTSS1 protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Colorectal cancer; Klotho; MTSS1; Metastasis; Prognosis; miR-15b