Knockdown of MRPL35 promotes cell apoptosis and inhibits cell proliferation in non-small-cell lung cancer

Abstract

Background Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC. Methods The expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting. Results MRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation. Conclusions The oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.

MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression

“…In our study, a high expression of MRPL35 in NSCLC patients was observed, and MRPL35 indicated poor prognosis in patients. Functionally, MRPL35 deficiency repressed NSCLC growth in vitro and in vivo, which was consistent with previous findings [ 16 ]. Moreover, we also found that MRPL35 silencing impaired cell invasion.…”

“…MRPL35 silencing promoted ROS‐induced autophagy and apoptosis and suppressed growth in colorectal cancer [ 15 ]. Moreover, MRPL35 suppressed the growth of NSCLC by repressing proliferation‐ and apoptosis‐related genes [ 16 ]. However, the role and mechanism of MRPL35 on glutamine metabolism in NSCLC are still vague.…”