title: miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A.
abstract: OBJECTIVE
  miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression.
  
  
  METHODS
  We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms.
  
  
  RESULTS
  miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer.
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. Oncology Institute, the Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Bojian
authors.initials: B
authors.lastname: Fei
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Song
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Ni
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. hzhwxsy@126.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D004195:Disease Models, Animal; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C549404:MIRN204 microRNA, human; D035683:MicroRNAs; C484191:RAB22A protein, human; D020691:rab GTP-Binding Proteins