<i>miR-4270</i> Modulates the Irradiation-Sensitivity of Nasopharyngeal Carcinoma Cells through Modulation of p53 <i>in Vivo</i>

Abstract

The lowered sensitivity to irradiation considerably impacted on the prognosis of nasopharyngeal carcinoma treatments. This study aimed to explore the functions of miR-4270 in nasopharyngeal carcinoma. Bioinformatic analysis was performed online accessing GSE139164 dataset to screen the top 30 differential microRNAs in nasopharyngeal carcinoma patients with radio-sensitivity. Cancer cell lines, 6-10B and 5-8F, were cultured and measured for expression of miR-4270 and TP53 (the gene of the tumor suppressor protein p53) with the normal nasopharyngeal epithelial cells as a control. The miR-4270 expression was regulated in cells via the introduction of miR-4270 inhibitor or mimic in different concentrations (25, 50, 100 nmol/L). Targetscan predicted the target of miR-4270 and the bindings while luciferase was used to confirm this. CCK8 methods were used to evaluate the irradiation sensitivity of the cells after exposure to increasing X-Ray irradiation. RT-PCR detected the RNA expression and Western blot examined the protein expression of p53. Flow cytometry detected the cell apoptosis rates respectively. miR-4270 is among the top differential microRNAs between the radio-sensitive and -resistant patients. In vivo, miR-4270 expression was lower in cancer cell lines. The inhibition of miR-4270 raised the cell sensitivity to irradiation. miR-4270 negatively mediated TP53 and targeted TP53. Additionally, p53 increased cell sensitivity to irradiation and modulated by miR-4270 in nasopharyngeal carcinoma cells. In conclusion, this study first reports that miR-4270 is lower in the radio-sensitive patients and modulated the irradiation-sensitivity of nasopharyngeal carcinoma cells through modulation of p53 in vivo.

Effect of miR-4270 Suppression on Migration in Hepatocellular Carcinoma Cell Line (HepG2)

“…Wang and coworkers [ 8 ] have displayed that the inhibition of miR-4270 reduces cell proliferation and apoptosis by inactivating NOTCH signaling pathway in Sertoli-cell-only syndrome patients. Moreover, Hao et al [ 17 ] have shown that miR-4270 directly targets P53 gene in the human neural progenitor cells.…”

MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells

“…Hao et al. reported that the levels of miR-4270 modulate the irradiation-sensitivity of nasopharyngeal carcinoma cells through modulation of p53 in vivo ( 46 ). Collectively, these results suggest that different levels of miR-4270 expression may be associated with different cancers and that miR-4270 likely has different functions.…”

“…Intriguingly, other studies have shown that circulating miR-4270 displays upregulated levels in metastatic gastric cancer and breast cancer patients, with the potential use of miR-4270 as a diagnostic or prognostic biomarker (44,45). Hao et al reported that the levels of miR-4270 modulate the irradiation-sensitivity of nasopharyngeal carcinoma cells through modulation of p53 in vivo (46). Collectively, these results suggest that different levels of miR-4270 expression may be associated with different cancers and that miR-4270 likely has different functions.…”

Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect

“…Upregulation of a TSG, a Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 ( PinX1 ), was found to activate the TP53/miRNA-200 axis, which in turn suppressed the EMT of CSC in NPC [ 133 ]. A recent study also demonstrated that the upregulation of miR-4270 in NPC has inhibited TP53 signalling [ 236 ]. In addition, cyclooxygenase-2 (COX-2)’s interaction with TP53 has been known to induce chemoresistance by inhibiting chemotherapeutic-induced cellular senescence [ 132 ].…”