miR-675-5p enhances tumorigenesis and metastasis of esophageal squamous cell carcinoma by targeting REPS2.
Recently H19 has been demonstrated to be up-regulated in esophageal squamous cell carcinoma (ESCC) and shown to be the precursor of miR-675 that encodes miR-675-5p conservatively. miR-675 is overexpressed in many human cancers; however, the function of miR-675-5p is largely unknown in ESCC. In this study, we found that miR-675-5p expression was significantly increased in ESCC tissues and cell lines and related with ESCC progression and poor prognosis. We also showed here that down-regulation of miR-675-5p in ESCC cells dramatically induced cell G1 arrest and reduced cell proliferation, colony formation, migration and invasion in vitro as well as tumorigenesis and tumor metastasis in vivo. We subsequently identified that REPS2 was a target gene of miR-675-5p. We found that inhibition of miR-675-5p up-regulated the expression of REPS2, inhibited RalBP1/RAC1/CDC42 signaling pathway. Inversely, interference of REPS2 abrogated the effect induced by miR-675-5p inhibition, which resembled the function of miR-675-5p up-regulation. Taken together, our findings suggested that miR-675-5p might play an oncogenic role in ESCC through RalBP1/RAC1/CDC42 signaling pathway by inhibiting REPS2 and might serve as a valuable prognostic biomarker and therapeutic target for ESCC patients.
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Yan-Wu
YW
Zhou
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Hang
H
Zhang
Institute of Medical Science, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Chao-Jun
CJ
Duan
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Yang
Y
Gao
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Yuan-Da
YD
Cheng
Institute of Medical Science, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Dan
D
He
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Rong
R
Li
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Chun-Fang
CF
Zhang
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002135:Calcium-Binding Proteins; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; C095637:RALBP1 protein, human; C489722:REPS2 protein, human; D034741:RNA, Small Interfering; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
RAC1/CDC42; REPS2; esophageal squamous cell carcinoma; miR-675-5p; microRNA