miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A

Abstract

Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b . Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b -PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b -PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress.

Two miRNA prognostic signatures of head and neck squamous cell carcinoma: A bioinformatic analysis based on the TCGA dataset

“…Abundant evidence had verified that miRNAs construct a complex network of genic expression and biologic pathway regulation, which has the function of prognosis and treatment target in many kinds of cancers . So far, several studies had proofed certain miRNAs with prognostic roles, such as miR‐654‐5p, miR‐125b, microRNA‐194‐5p, miR‐196b, miR‐548b, and so on. Nevertheless, the majority of formerly researches have concentrated on unimolecular incidents, limited cases, nonstandardized detective technique, and so on.…”

The miR-372-ZBTB7A Oncogenic Axis Suppresses TRAIL-R2 Associated Drug Sensitivity in Oral Carcinoma

“…Western blot analysis followed protocols that we previously established using various primary antibodies (Table S4) and a range of secondary antibodies (Table S5) (4,9). GAPDH was used as the internal control for Western blotting.…”

“…When develop new strategies that block HNSCC development, a molecular understanding of HNSCC pathogenesis is important (1). Over the last decade, many studies have indicated that miRNAs and theirs targeted genes are highly associated with OSCC promotion and progression (3)(4)(5)(6)(7)(8)(9).…”

NF-κB-Mediated lncRNA AC007271.3 as A ceRNA Promotes Carcinogenesis of Oral Squamous Cell Carcinoma by Regulating Slug

“…It had reported that miR-125b-2-3p was down-regulated in hepatocellular carcinoma [25] and small cell osteosarcoma [26] but upregulated in tumor stroma of colon cancer [27] . In OSCC, although miR-125b was found to inhibit the progression of OSCC [28] , the function of miR-125b-2-3p is still uncertain. In our study, we con rmed that the expression levels of miR-125b-2-3p were negatively correlated with TNM classi cation and lymph node metastasis in OSCC patients.…”