Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells.
Both miRNAs (miRs) and connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, whereas the miRs regulating Cx43 expression in breast cancer cells were still obscure. In the present study, we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3'-untranslated region (3'-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF cells potentiated the migration activity, whereas additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues compared with the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.
Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China mingjia1001@sina.com.
Jia
J
Ming
Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China.
Yan
Y
Zhou
Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China.
Junze
J
Du
Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Shenghao
S
Fan
Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Beibei
B
Pan
Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Yinhuan
Y
Wang
Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China.
Lingjun
L
Fan
Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China.
Jun
J
Jiang
D020413:3' Untranslated Regions; D001483:Base Sequence; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018031:Connexin 43 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology
D020413:3' Untranslated Regions; D018031:Connexin 43; C533896:MIRN200 microRNA, human; D035683:MicroRNAs
3′-untranslated region (3′-UTR); breast cancer; connexin 43 (Cx43); metastasis; micro ribonucleic acid (miR)-1; micro ribonucleic acid (miR)-200a