DRAM2 acts as an oncogene in non-small cell lung cancer and suppresses the expression of p53

Abstract

BackgroundDamage-regulated autophagy modulator 2(DRAM2) is associated with autophagy processes. However, the role of DRAM2 in the progression of human neoplasms is still unknown. Here, we show that DRAM2 may act as an oncogenic regulator in non-small cell lung cancer (NSCLC).MethodsTumor specimens from 259 NSCLC patients were collected and analyzed. Transwell migration, cell cycle analysis, MTT and colony formation assays were performed to determine the effect of DRAM2 overexpression and knockdown on NSCLC-cell migration and proliferation. Western blotting confirmed the expression of DRAM2, p53, and the other involved proteins.ResultsDRAM2 was preferentially upregulated in NSCLC tissues and higher expression of DRAM2 in NSCLC correlated with tumor node metastases stage and lymph node metastasis. Additionally, DRAM2 overexpression promoted cell metastasis and proliferation in vitro, while knockdown of DRAM2 expression yielded opposite result. Furthermore, DRAM2 overexpression increased the expression of proteins RAC1, RHOA, RHOC, ROCK1, and decreased RHOB expression, all of which are cell migration factors. DRAM2 overexpression also increased proteins CDK4, CyclinD3, and decreased p27 expression, all of which are cell cycle-related factors. Consistently knocked down DRAM2 had the opposite effect. We also found that DRAM2 expression was negatively correlated to p53 expression. Knockdown of DRAM2 caused an increase of p53 and p21 expression, and overexpression of p53 caused a decrease of DRAM2 expression. Finally, absence of p53 did not influence the function of DRAM2 in NSCLC, but overexpression of p53 repressed its function.ConclusionsDRAM2 plays an oncogenic role in NSCLC via regulating p53 expression. Therefore, DRAM2 may act as an oncogene in NSCLC and could serve as a prognostic factor and potential target for NSCLC treatment.

RETRACTED: KCNQ1OT1 accelerates gastric cancer progression via miR-4319/DRAM2 axis

“…14 DRAM2 was found serve as an oncogene in non-small cell lung cancer and retinoblastoma. 15,16 We showed overexpression of DRAM2 stimulates GC cell growth by inhibiting cell apoptosis and facilitating cell cycle, and could reverse the roles of sh-KCNQ1OT1 on GC cell behaviors. There is limitation in this work which is we did not recruit GC patients into our work so that we are unable to validate expression level of the triplet network and their corrections in GC tissues.…”

The Clinical Spectrum and Disease Course of DRAM2 Retinopathy

“…DRAM2 (MIM 613360) encodes a DNA-damage regulated autophagy modulator 2 (DRAM2), also known as transmembrane protein 77 (TMEM77), a 266 amino acid transmembrane protein containing six putative transmembrane domains [6,7]. It is ubiquitously expressed in numerous tissues, including the lymph nodes, spleen, heart, and placenta [8,9], where it localizes to lysosomal membranes and is thought to play a role in the autophagy process and tumor suppression [6,7,10,11]. Immunohistochemical analysis of the retina revealed that DRAM2 localizes to the inner segments of the photoreceptors and the apical surface of the RPE cells [12].…”

Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review)

“…Higher expression levels of DRAM2 in NSCLC are associated with TNM stage and lymph node metastasis. As an oncogene, interference with DRAM2 can induce upregulation of p53 and p21 expression in NSCLC cells ( 89 ). Quercetin, a chemical extracted from a traditional Chinese drug, has been shown to promote HDGF secretion and to induce autophagy.…”