MicroRNA-124-3p inhibits the growth and metastasis of nasopharyngeal carcinoma cells by targeting STAT3

Abstract

The present study investigated the effects of microRNA-124-3p (miR-124-3p) expression on nasopharyngeal carcinoma (NPC) cells and its relevant mechanism. A total of 90 NPC tissues and 85 postnasal catarrh tissues were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect tissue samples and expression of miR-124-3p in CNE1, CNE2, SUNE1, H0NE1, 5-8F, 6-10B and C666-1 NPC cell line and immortalized nasopharyngeal epithelial cells line (NP69). Overexpressed miRNA-124-3p in CNE-2 was downregulated, and low-expressed miRNA‑124-3p in C666-1 was upregulated by liposome-mediated transfection. Cell Counting Kit-8 (CCK-8), flow cytometry, the scratch test, Transwell migration assay and Boyden chamber assays were used to detect cell proliferation, apoptosis, migration and invasion. The target gene of miRNA-124-3 calculated by bioinformatics was further determined using dual-luciferase system. Protein levels of the signal transducers and activators of transcription 3 (STAT3), phospho-STAT3 (p-STAT3), mouse anti-human cyclin D2 (CCND2) and matrix metalloproteinase-2 (MMP-2) were tested by western blotting. miRNA-124-3p expression in NPC was markedly downregulated compared to postnasal catarrh tissues (P<0.001); miRNA-124-3p expression showed close linkage with clinical stages, regional lymph node involvement and T stages (all P<0.001). miRNA-124-3p expression was lower in the 7 NPC cell lines than NP69 cells (all P<0.05). After upregulation of miR-124-3p, proliferation, apoptosis, migration and invasion of C666-1 cells were suppressed; while after downregulation of miR-124-3p, CNE2 cells were increased (all P<0.05). Expression of STAT3, p-STAT3, CCND2 and MMP-2 in C666-1 cells was decreased after transfection with miRNA-124-3p, and the above protein expression in CNE-2 cells was increased after inhibition of miRNA-124-3p (all P<0.05). To sum up, this study shows that miR-124-3p may negatively regulate the transcription of the STAT3 by interfering with its 3'UTR, and the degradation of STAT3 affects its downstream expression of such as p-STAT3, CCND2 and MMP-2, thereby promoting NPC cells apoptosis and inhibiting proliferation, migration and invasion of NPC cells.

miR-124 suppresses proliferation and invasion of nasopharyngeal carcinoma cells through the Wnt/&beta;-catenin signaling pathway by targeting Capn4

“…In addition, the overexpression of miR-124 resulted in the inhibition of cell proliferation and invasion in NPC cells. In agreement with our findings, previous studies revealed that overexpression of miR-124 dramatically suppressed cell proliferation, colony formation, migration, and invasion of NPC by targeting STAT3 or Foxq1 12,13. All these findings suggest that miR-124 functions as a tumor suppressor in NPC.…”

“…In consistent with our findings, Cai et al26 revealed that miR-124 suppressed the migration and invasion of glioma cells by targeting Capn4. Previous studies also have demonstrated that miR-124 inhibited the proliferation and invasion of NPC cells by modulating its functional targets, such as STAT3 and Foxq1 12,13. All these findings suggest that miR-124 regulates different targets in NPC.…”

“…It is noteworthy that miR-124 generally acts as a tumor suppressor in multiple cancers, such as breast cancer,10 colorectal carcinoma,11 and NPC 12. Moreover, downregulation of miR-124 has been reported in NPC, and restoration of expression of miR-124 suppressed the proliferation, migration, and invasion of NPC cells 12,13. However, the mechanism by which miR-124 regulates NPC progression needs to be further investigated.…”

Midazolam inhibits proliferation and accelerates apoptosis of hepatocellular carcinoma cells by elevating microRNA‐124‐3p and suppressing PIM‐1

“…Another significant result of our study is that the up‐regulated miR‐124‐3p could accelerate the apoptosis as well as cell cycles in HCC. In line with this outcome, the promotive impacts of miR‐124‐3p on apoptosis of nasopharyngeal carcinoma cells have been reported in an existing research . In addition, Zhang et al have also discovered that the overexpression of miR‐124‐3p has the ability to repress the apoptosis and cell cycle arrest in glioblastoma multiforme through regulating NRP‐1 .…”

Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment

“…The dysregulation of p53 or its associated miRNAs has been reported to confer resistance against apoptosis in cancer cells. Moreover, apoptosis is induced by the overexpression of miR-101 in human BCC via modulating JAK2 [115] and by miR-124-3p in nasopharyngeal carcinoma via modulating STAT3 and its downstream targets [116]. Yan et al [114] have demonstrated that upregulation of miR-17-92 cluster in tumor cells can evade hypoxia-triggered apoptosis.…”