MicroRNA-93 regulates cyclin G2 expression and plays an oncogenic role in laryngeal squamous cell carcinoma

Abstract

microRNA93 (miR-93) is expressed in the miR‑106b-25 cluster, located in intron 13 of the MCM7 gene. Our previous study found that miR-93 was significantly upregulated in laryngeal squamous cell carcinoma (LSCC), and cyclin G2 (CCNG2) was a potential target of miR-93 in LSCC. However, the possible functions and molecular mechanisms of miR-93 in LSCC remain unknown. In the present study, we show that the level of CCNG2 protein expression was significantly lower in LSCC cancer tissue than normal tissues. The level of CCNG2 was correlated with clinical stages, lymph node metastasis and histological grade. We further show that the expression level of miR-93 was inversely correlated with CCNG2 expression in clinical specimens. Furthermore, gain-of-function assays revealed that miR-93 promoted cell proliferation, decreased apoptosis rates, induced cell cycle arrest and promoted cell migration and invasion, whereas silencing of miR-93 attenuated these carcinogenic processes. In addition, overexpression of miR-93 in Hep-2 cells could reduce the mRNA and protein levels of CCNG2, whereas silencing of miR-93 in Hep-2 cells significantly increased CCNG2 expression. A luciferase assay verified that miR-93 could bind to the 3' untranslated region of CCNG2. Importantly, ectopic expression of CCNG2 in miR-93 cells rescued the effect of miR-93 on LSCC proliferation. Knockdown of CCNG2 promoted cell proliferation resembling that of miR-93 overexpression. These findings demonstrated that miR-93 promotes tumor growth by directly suppressing CCNG2. Taken together, these results suggested that this newly identified miR-93-CCNG2 axis may be involved in LSCC proliferation and progression. Our findings provide novel potential targets for LSCC therapy and prognosis.

Unveiling MYCN regulatory networks in neuroblastoma via integrative analysis of heterogeneous genomics data

“…miR-93-5p has been documented to play a role as an oncogenic miRNA in many tumor types [64–66], but has not been investigated in NB. miR-93-5p is hosted in MCM7, which is regulated by MYCN, and is also predicted to target MYCN (confidence score: 1.0).…”

MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer

“…28 MiR-93 was also reported to function as a tumor promoter via regulating diversity of tumor-suppressor genes such as NRF2, 29 Dab2 30 and cyclin G2. 31 More interestingly, certain researches revealed that either miR-106b or miR-93 could directly target one common gene named PTEN in many other cancers. 32, 33 In our research, we found that PTEN was the direct target of both miR-106b and miR-93.…”

A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in Breast Cancer

“…Oncogenic function of miR-93 is also reported in prostate cancer, ovarian cancer, lung cancer, head and neck squamous cell carcinoma, and non–small cell lung cancer [41], [42], [43], [44], [45]. It is also documented that miR-93 promotes glioma through regulation of AKT and IL8 [46].…”