MiR-125b acts as an oncogene in glioblastoma cells and inhibits cell apoptosis through p53 and p38MAPK-independent pathways

Abstract

Background:We have recently identified miR-125b upregulation in glioblastoma (GMB). The aim of this study is to determine the correlation between miR-125b expression and malignant grades of glioma and the genes targeted by miR-125b.Methods:Real-time PCR was employed to measure the expression level of miR-125b. Cell viability was evaluated by cell growth and colony formation in soft-agar assays. Cell apoptosis was determined by Hoechst 33342 staining and AnnexinV-FITC assay. The Luciferase assay was used to confirm the actual binding sites of p38MAPK mRNA. Western blot was used to detect the gene expression level.Results:The expression level of miR-125b is positively correlated with the malignant grade of glioma. Ectopic expression of miR-125b promotes the proliferation of GMB cells. Knockdown of endogenous miR-125b inhibits cell proliferation and promotes cell apoptosis. Further studies reveal that p53 is regulated by miR-125b. However, downregulation of the endogenous miR-125b also results in p53-independent apoptotic pathway leading to apoptosis in p53 mutated U251 cells and p53 knockdown U87 cells. Moreover, p38MAPK is also regulated by miR-125b and downregulation of miR-125b activates the p38MAPK-induced mitochondria apoptotic pathway.Conclusion:High-level expression of miR-125b is associated with poor outcomes of GMB. MiR-125b may have an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis.

MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis

“…In contrast, cell proliferation, clone formation, migration, and invasion were significantly promoted in MKN-45 cells with transfected MiR-125bm; therefore, we explored the tumorpromoting role for MiR-125b in gastric cancer for the first time and possible evidence of the potential usefulness of MiR-125b in MiRNA-based cancer therapy. MiR-125b has various regulating pathways in the process of cell proliferation, differentiation, and apoptosis, such as inhibiting p53-induced apoptosis during development and the stress response [14], inhibiting cell apoptosis through p53 and p38-MAPK-independent pathways in glioblastoma cells [21], targeting EPO and EPOR to correlate with metastatic potential, and expressing ERBB2/HER2 in breast cancer [22]. In this study, to explore the potential targets of MiR125b that might influence proliferation and migration ability of gastric cancer cells, PPP1CA was found among the potential targets of the MiR-125b combination predicted by TargetScan, Pictar-Vert, and Microrna.…”

<p>The Emerging Roles of miR-125b in Cancers</p>

“…The dysregulation of miR-125b is shown in Table 1. Upregulation of miR-125b as an oncogene has been reported in various cancers: nasopharyngeal carcinoma (NPC), 13,14 retinoblastoma (RB), 15 glioblastoma (GBM), [16][17][18][19][20] poorly differentiated non-small-cell lung cancer (NSCLC), 21 acute lymphoblastic leukemia (ALL), 22 acute myeloid leukemia (AML), 23 and gastric cancer. [24][25][26] On the other hand, miR-125b, as a tumor suppressor, is downregulated in the following cancers: non-small-cell lung cancer (NSCLC), 27 esophageal squamous cell carcinoma (ESCC), 28,29 anaplastic thyroid cancer, 30 bladder cancer, [31][32][33][34][35] hepatocellular carcinoma (HCC), [36][37][38][39] melanoma, 40,41 ovarian cancer, [42][43][44] osteosarcoma, [45][46][47] chondrosarcoma, 48 breast cancer, [49][50][51][52][53][54][55] gallbladder cancer (GBC), 56 endometrioid endometrial cancer (EEC),…”

MicroRNA-125b targeted STAT3 to inhibit laryngeal squamous cell carcinoma cell growth and motility

“…In prostate cancer, miR-125b enhanced prostatic xenograft tumors proliferation through downregulation of p53 and Bcl-2-binding component 3 (30). In glioblastoma, Wu et al (26) verified that miR-125b was upregulated and significantly associated with poor prognosis. miR-125b functioned as an oncogene by suppressing cellular apoptosis and enhancing cellular proliferation.…”

“…miR-125b has been observed to be downregulated in various types of cancer, including oral cancer (23), bladder cancer (18), liver cancer (19), osteosarcoma (20) and endometrial cancer (24). Previous studies have also demonstrated that miR-125b was upregulated in a number of types of cancer, including prostate cancer (25), glioblastoma (26) and pediatric acute promyelocytic leukemia (27). However, there are no studies investigating the expression of miR-125b in LSCC.…”