MiR-95 induces proliferation and chemo- or radioresistance through directly targeting sorting nexin1 (SNX1) in non-small cell lung cancer.
MicroRNAs are emerging as a class of small regulatory RNAs whose specific roles and significant functions in the majority of carcinomas have yet to be entirely illustrated. The aim of this study is to explore the effect of miR-95 and determine whether miR-95 could be a potential therapeutic target for human non-small cell lung cancer. First of all, our study showed that miR-95 was highly expressed in both NSCLC cell lines (compared with normal cells) and tumor tissues (compared with corresponding normal tissues), whereas the protein level of SNX1 was downregulated in NSCLC cell lines. Next, we found that ectopic overexpression of miR-95 in A549 or H226 contributed to tumor growth in xenograft mouse models. In addition, the results also indicated that upregulation of miR-95 could significantly enhance the susceptibilities of NSCLC cells to chemo- or radiotherapy. Furthermore, using the luciferase reporter, we demonstrated that SNX1 is a direct target of miR-95. Meanwhile, overexpression of SNX1 could abrogate the growth of NSCLC cells induced by miR-95. Taken together, these results suggest that miR-95 functions as an oncogene role in NSCLC cells by directly targeting SNX1.
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, People's Republic of China.
Xiaochun
X
Chen
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, People's Republic of China.
Shaomu
S
Chen
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, People's Republic of China.
Weijie
W
Hang
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, People's Republic of China.
Haitao
H
Huang
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, People's Republic of China. Electronic address: haitaomasoochow@163.com.
Haitao
H
Ma
D000818:Animals; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011836:Radiation Tolerance / Q000235:genetics*; D058305:Sorting Nexins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
C575854:MIRN95 microRNA, human; D035683:MicroRNAs; C513978:SNX1 protein, human; D058305:Sorting Nexins
Chemotherapy; NSCLC; Radiotherapy; SNX1; Tumor growth; miR-95