MiR-761 Promotes Progression and Metastasis of Non-Small Cell Lung Cancer by Targeting ING4 and TIMP2.
OBJECTIVE
The aim of this study was to investigate the role of microRNA miR-761 in the progression and metastasis of non-small cell lung cancer (NSCLC), and the mechanisms by which miR-761 regulates cell proliferation and metastatic activity of NSCLC cell lines.


METHODS
Quantitative real-time PCR (qRT-PCR) was used to assess miR-761 expression in NSCLC serum and tissue. MTT, wound healing, and transwell assays were performed to examine the role of miR-761 in regulation of cell proliferation and metastatic activity in NSCLC cell lines. In addition, the correlations of miR-761 expression with clinical-pathologic factors were statistically analyzed. Finally, we investigated whether miR-761 promotes proliferation and metastasis in NSCLC cell lines by targeting ING4 (inhibitor of growth family, member 4) and TIMP2 (tissue inhibitor of metalloproteinase 2).


RESULTS
MiR-761 was significantly upregulated in both NSCLC serum and tissues as compared to normal participants and paired noncancerous tissues respectively. Ectopic expression of miR-761 promoted cell proliferation and metastasis in H460 cells, while miR-761 inhibitor reduced proliferation rates and metastasis in H23 cells. Furthermore, luciferase reporter assay and functional analyses indicated that miR-761 directly targeted ING4 and TIMP2.


CONCLUSIONS
miR-761 promotes progression and metastasis of NSCLC by targeting ING4 and TIMP2.
Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
An
A
Yan
Chunyu
C
Yang
Zhibo
Z
Chen
Chunhong
C
Li
Li
L
Cai
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D035683:MicroRNAs; C560823:TIMP2 protein, human; D025521:Tumor Suppressor Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2