miR‑125a is upregulated in cancer stem‑like cells derived from TW01 and is responsible for maintaining stemness by inhibiting p53

Abstract

microRNA (miR)-125a and miR-125b were demonstrated to translationally and transcriptionally inhibit the mRNA level of p53 following the induction of chemo-reagents in our previous report. As a small subpopulation of nasopharyngeal carcinoma (NPC), cancer stem-like cells (CSCs) function critically in multi-malignant behaviors, including tumorigenesis and metastasis; however, the expression pattern and regulatory role of miR-125a, miR-125b and p53 in CSCs derived from NPC remain unclear. In order to investigate the potential regulatory role of miR-125 on p53, firstly CSCs was isolated from TW01 by culturing in serum-free medium. The stemness of isolated CSCs was examined via self-renewal capacity and side population assays. Following this, the miR-125a, miR-125b and p53 mRNA levels were evaluated via reverse-transcription quantitative polymerase chain reaction. Following the transfections of wild-type p53 or p53 without DNA binding activity (p53-mutR 248Q) into TW01 or CSCs, Chromatin Immunoprecipitation (ChIP), and cell cycle analyses using flow cytometry or Cell Counting Kit-8 assays were performed. Notably, it was determined that miR-125a was significantly upregulated in CSCs derived from TW01, but not miR-125b, and the mRNA and protein levels of p53 were downregulated. The transfection of p53 significantly decreased the cell viability and stopped cell cycle at the G 0 /G 1 phases in TW01 and CSCs. The ChIP assay confirmed that the ectopic expression of wild-type p53 transcriptionally regulates its downstream gene, p21, but not B-cell lymphoma 2 nor Sco2. Taken together, the results of the present study indicated that p53 regulates CSCs via its DNA binding activity and potentially, in CSCs, miR-125a regulates the expression of p53, maintaining stemness.

Elevated circulating lnc‐ANRIL/miR‐125a axis level predicts higher risk, more severe disease condition, and worse prognosis of sepsis

“…These mechanistic experiments indicate that miR‐125a is a crucial regulator in inflammation and immune responses, which might explain the results in our study that miR‐125a plasma expression could predict sepsis risk, and was negatively correlated with severity and pro‐inflammatory cytokines levels in sepsis patients. In addition, there is a report showing that U6 might not be an appropriate internal reference for miRNAs detection; however, for circulating miR‐125a expression detection, there are still mounting studies using U6 as an internal reference …”

“…Univariate and multivariate Cox's proportional hazards model analyses of factors affecting accumulating survival sepsis risk, and was negatively correlated with severity and pro-inflammatory cytokines levels in sepsis patients. In addition, there is a report showing that U6 might not be an appropriate internal reference for miRNAs detection; however, for circulating miR-125a expression detection, there are still mounting studies using U6 as an internal reference 12,[30][31][32].…”

Low expression of miR‑125a‑5p is associated with poor prognosis in patients with gastric cancer

“…Therefore, even though there were no changes in GC cell proliferation, migratory and invasive ability in vitro , it is possible that miR-125a-5p functions as a tumor suppressor in vivo by regulating the tumor microenvironment, including effects on tumor angiogenesis. It is still possible that miR-125a-5p may regulate stemness (37), a critical feature of tumor formation, just like the tumor size. Therefore, in vivo experiments assessing the effect of miR-125a-5p on tumor growth and metastasis are required.…”

Target Analysis and Mechanism of Podophyllotoxin in the Treatment of Triple-Negative Breast Cancer

“…According to our analyses, we found that the identified genes are closely related to the cell cycle pathway. Several reports indicated that the upstream and downstream proteins of the cell cycle pathway are regulated by P53 ( Zhang et al, 2018 ; Chen et al, 2019 ; Wang et al, 2020 ). Within 24 h after treatment with 0.75 μmol/L podophyllotoxin, we observed the effect of podophyllotoxin on the mRNA level of identified genes in MD-MBA-231 and MD-MBA-468 cells.…”