Knockdown of response gene to complement 32 (RGC32) induces apoptosis and inhibits cell growth, migration, and invasion in human lung cancer cells.
Response gene to complement 32 (RGC32) is a novel protein originally identified as a cell cycle activator and has been demonstrated to be overexpressed in a variety of human malignancies, including lung cancer. However, the potential role of RGC32 in lung cancer initiation and progression remains to be elucidated. In the present study, RNA interference mediated by plasmid expressing RGC32 short-hairpin RNA (shRNA) was utilized to knockdown RGC32 expression in human lung cancer LTE cells. We found that the mRNA and protein expression levels of RGC32 were significantly decreased in RGC32-specific shRNA-transfected cells in comparison with the untransfected and control shRNA-transfected cells. Furthermore, knockdown of RGC32 dramatically reduced cell proliferation, colony formation, and invasion and migration capacities of LTE cells in vitro. Specific down-regulation of RGC32 caused G0/G1 cell cycle arrest and eventual apoptosis. Meanwhile, Western blot analysis indicated that cells with stably knockdown of RGC32 showed decreased expression levels of Cyclin D1, Cyclin E, Bcl-2, matrix metalloproteinase (MMP)-2, and MMP-9, but increased expression levels of activate caspase-3, Bax, and cleaved poly (ADP-ribose) polymerase (PARP) in comparison with control shRNA-transfected cells. Taken together, our data suggest that RGC32 is involved in tumorigenesis of human lung cancer and may serve as a promising therapeutic target for lung cancer.
Department of Thoracic Surgery, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Ran
R
Xu
Chao
C
Shang
Jungang
J
Zhao
Yun
Y
Han
Jun
J
Liu
Kuanbing
K
Chen
Wenjun
W
Shi
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C115049:RGCC protein, human; D012333:RNA, Messenger