Knockdown of response gene to complement 32 (RGC32) induces apoptosis and inhibits cell growth, migration, and invasion in human lung cancer cells

Abstract

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.

Expression of RGC32 in human normal and preeclamptic placentas and its role in trophoblast cell invasion and migration

“…RGC32 has been demonstrated to be able to regulate the expression and activities of MMP-2 and MMP-9 [21,22]. In addition, MMPs, Fig.…”

“…Accumulating studies have demonstrated that RGC32 expression is dysregulated in human malignancies [16,20]. Recent studies have reported that RGC32 may regulate cancer cell migration and invasion [21,22]. As the human EVT cell line HTR8/SVneo has been widely used to study trophoblast biology [28,29], we further investigated the function of RGC32 in HTR8/SVneo.…”

“…Accumulating studies show that RGC32 expression was dysregulated in many human cancers [17e20], which may contribute to tumorigenesis and progression. Recent study has identified that RGC32 can regulate the migration and invasion of tumor cells by affecting the expression and function of matrix metalloproteinases (MMPs) [21,22]. Meanwhile, MMPs have been demonstrated to be involved in trophoblast invasion and migration [9,23].…”

RGC32 induces epithelial-mesenchymal transition by activating the Smad/Sip1 signaling pathway in CRC

“…It plays important roles in the regulation of cell differentiation, angiogenesis, migration, and invasion456. In addition, emerging evidence has revealed that RGC32 is involved in lung cancer7, breast cancer8, hepatic steatosis9, and multiple sclerosis10. However, little is known about its function in CRC.…”

Oncogenic gene RGC‐32 is a direct target of miR‐26b and facilitates tongue squamous cell carcinoma aggressiveness through EMT and PI3K/AKT signalling

“…[12][13][14][15][16] A considerable amount of literatures have been published on regulatory effects of RGC-32 in a variety of non-cancerous diseases, concerning vascular diseases, [17][18][19] Alzheimer's Disease, 20 obesity, 21 diabetic retinopathy, 22 autoimmune encephalomyelitis, 23 renal ischemia reperfusion injury, 24 preeclampsia 25 and other non-tumour diseases. In addition to its mediating role in non-cancer, essential roles of it were identified to facilitate the progressions of numerous malignancies, namely ovarian cancer, 26,27 colon cancer, 28,29 prostate cancer, 30 lung cancer, 31,32 breast carcinoma 33 and pancreatic cancer. 34,35 On the contrary, in the literature on Saigusa et al, the relative importance of RGC-32 is debated that RGC-32 emerges as a novel p53-inducible gene, by mediating the arrest of mitotic progression and possible behaves as a tumour-suppressor for glioma.…”