MiR‐16‐5p is frequently down‐regulated in astrocytic gliomas and modulates glioma cell proliferation, apoptosis and response to cytotoxic therapy

Abstract

Aims Aberrant expression of microRNAs (miRNAs) is frequent in various cancers including gliomas. We aimed to characterize the role of miR‐16‐5p as a candidate tumour suppressor miRNA in gliomas. Methods Real‐time PCR‐based approaches were used for miRNA and mRNA expression profiling of glioma and non‐neoplastic brain tissues as well as glioma cell lines. Protein levels were determined by Western blotting. In vitro analyses were performed following overexpression of miR‐16‐5p, trichostatin A (TSA) treatment, and siRNA‐mediated knock‐down of HDAC3 in glioma cells. Effects of miR‐16‐5p on glioma cell viability, apoptosis and response to irradiation and temozolomide (TMZ) were assessed. Results Expression of miR‐16‐5p was reduced relative to control brain tissue in isocitrate dehydrogenase (IDH)‐mutant astrocytomas of World Health Organization (WHO) grades II, III and IV, and a subset of IDH‐wildtype glioblastomas WHO grade IV. MiR‐16‐5p expression was lower in IDH‐mutant than in IDH‐wildtype gliomas, and down‐regulated in IDH‐wildtype glioma lines. MiR‐16‐5p overexpression reduced expression of important cell cycle and apoptosis regulators in glioma cells, including CDK6, CDC25A, CCND3, CCNE1, WEE1, CHEK1, BCL2 and MCL1. In line, CDK6, WEE1, CHEK1, BCL2 and MCL1 transcript levels were increased in WHO grade III or IV gliomas. TSA treatment and HDAC3 knockdown in glioma cells induced miR‐16‐5p up‐regulation and reduced expression of its targets. Moreover, miR‐16‐5p overexpression inhibited proliferation and induced apoptosis in various glioma cell lines and increased sensitivity of A172 glioma cells to irradiation and TMZ. Conclusion Reduced expression of miR‐16‐5p contributes to glioma cell proliferation, survival and resistance to cytotoxic therapy.

<p>Tanshinone IIA Suppresses Glioma Cell Proliferation, Migration and Invasion Both in vitro and in vivo Partially Through miR-16-5p/Talin-1 (TLN1) Axis</p>

“…There were quite a few of researches demonstrating miR-16-5p as tumor suppressor in glioma. Consistent with previous studies, 16,17 we observed a downregulation of miR-16-5p in human glioblastoma cells. While miR-16-5p level began to be upregulated in response to TIIA treatment, which suggested that TIIA exerting anti-glioma role was partially attributed to miR-16-5p upregulation.…”

“…15 In glioma, miR-16-5p participates in almost all cell events, such as proliferation, metastasis, apoptosis, radiosensitivity and chemoresistance. 16,17 Thus, this miRNA has been suggested as a potential biomarker in the diagnosis and treatment of glioma. 18,19 In this study, we intended to investigate the contribution of miR-16-5p to the role of TIIA in malignant behaviors of human glioma cells, as well as its functional downstream target.…”

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients

“…Of these, the top ve miRNAs were miR-16-5p, miR-29a-3p, miR-34c-5p, miR-32-5p and miR-490-5p. MiR-16-5p was reportedly downregulated in breast cancer [76], hepatocellular carcinoma [77] and glioma [78], in agreement with our ndings. Overall, miR-29a-3p has been reported to function as a tumour suppressor and is downregulated in many types of cancers, such as thyroid carcinoma [32], colorectal carcinoma [79] and hepatocellular carcinoma [80].The downregulation of miR-34c-5p has been reported in several types of cancer, such as leukaemia [57] and osteosarcoma [58], and it has been closely associated with poor prognosis.…”

“…The expression of miR-452-5p was signi cantly increased in 387 clinical lung squamous cell carcinoma specimens [37] and renal cell carcinoma tissues [38], whereas it was downregulated in 1007 prostate cancer samples [39]. MiR- 16-5p has been proposed to function as a tumour suppressor and it was downregulated in non-small cell lung cancer cell lines [40], breast cancer samples [41], hepatocellular carcinoma tissues [42], chordoma tissues [43] and glioma tissues [44]. It was also downregulated in the plasma of gastric cancer patients [45].…”

Comprehensive analysis of a long non‑coding RNA‑associated competing endogenous RNA network in glioma

“…WEE1, a regulator of the G 2 checkpoint in GBM cells, was associated with malignancy and poor outcomes of patients with GBM (49). CDC25A and CHEK1 are significant regulators of the cell cycle and apoptosis in glioma cells (50).…”