MiRNA 17 family regulates cisplatin-resistant and metastasis by targeting TGFbetaR2 in NSCLC.
MicroRNAs (miRNAs) have been proven to play crucial roles in cancer, including tumor chemotherapy resistance and metastasis of non-small-cell lung cancer (NSCLC). TGFβ signal pathway abnormality is widely found in cancer and correlates with tumor proliferation, apoptosis and metastasis. Here, miR-17, 20a, 20b were detected down-regulated in A549/DDP cells (cisplatin resistance) compared with A549 cells (cisplatin sensitive). Over-expression of miR-17, 20a, 20b can not only decrease cisplatin-resistant but also reduce migration by inhibiting epithelial-to-mesenchymal transition (EMT) in A549/DDP cells. These functions of miR-17, 20a, 20b may be caused at least in part via inhibition of TGFβ signal pathway, as miR-17, 20a, 20b are shown to directly target and repress TGF-beta receptor 2 (TGFβR2) which is an important component of TGFβ signal pathway. Consequently, our study suggests that miRNA 17 family (including miR-17, 20a, 20b) can act as TGFβR2 suppressor for reversing cisplatin-resistant and suppressing metastasis in NSCLC.
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Zeyong
Z
Jiang
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Jun
J
Yin
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Wenfan
W
Fu
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Yijun
Y
Mo
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Youguang
Y
Pan
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Lu
L
Dai
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Haoda
H
Huang
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Siwen
S
Li
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China.
Jian
J
Zhao
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D002945:Cisplatin