miR‑133a, directly targeted USP39, suppresses cell proliferation and predicts prognosis of gastric cancer

Abstract

Gastric cancer has high incidence and mortality, and the mortality ranks second only to lung cancer. Downregulation of miR-133a has been observed in certain types of tumors, and it is involved in gastric cancer. The aim of the present study was to explore the molecular mechanisms of miR-133a and ubiquitin-specific protease 39 (USP39) in gastric cancer. Western blot analysis and RT-PCR were employed to measure miR-133a and USP39 expression. To confirm whether miR-133a targeted USP39, we conducted a luciferase reporter assay. We utilized 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay to detect the effects of miR-133a on gastric cell proliferation. miR-133a was significantly downregulated in cancer tissues and cell lines (HGC-27 and MGC-803), while the expression level of USP39 was higher in tumor tissues than in paracancerous tissues. Upregulated expression of miR-133a and/or USP39 downregulation could inhibit cell proliferation in gastric cancer cells. Furthermore, USP39 was identified as a direct target of miR-133a and the inverse relationship between them was also observed. USP39 was a firsthand target of miR-133a and there was a negative correlation between them. In addition, a low expression of miR-133a or overexpression of USP39 predicted poor prognosis. In conclusion, miR-133a may be a novel therapeutic target of microRNA-mediated suppression of cell proliferation in CC, but the role of the miR-133a/USP39 axis in CC progression needs further study.

The role of deubiquitinating enzymes in gastric cancer (Review)

“…As USP39 is upregulated in certain types of cancer, and hyperproliferation is a hallmark of cancer, USP39 may represent a potential therapeutic target for the treatment of several cancer types (73). By contrast, miR-133a expression was inversely correlated with USP39, which it directly targets by binding at the 3′-untranslated region; the high expression rate of USP39 indicated a longer survival time for patients (74).…”

Emerging roles of MiR-133a in human cancers

“…MiRNAs, a class of noncoding RNA (ncRNA) about 22-nucleotide RNAs in size, are highly conserved molecules regulating gene expression post-transcriptionally by binding to the 3'-untranslated region (3'-UTR) of target message RNAs (mRNAs) 2 and participating in tumorigenesis, proliferation, invasion and drug resistance in cancer 3 . Among the miRNAs, miR-133a has been considered as a tumor suppressor and a biomarker for prognosis of various cancers, such as osteosarcoma 4 , esophageal cancer (EC) 5 , colorectal cancer (CRC) 6 , non-small cell lung cancer (NSCLC) 7 , bladder cancer 8 , breast cancer 9 and gastric cancer (GC) 10 .…”

miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer

“…miRNAs have also been reported to be associated with the initiation of chief cell transdifferentiation and apoptosis . miR‐133a has been reported to directly target eIF4A1, SENP1, EGFR , and USP39 genes and regulate their expression, and then participate in the pathophysiological processes of colorectal cancer, nonsmall‐cell lung cancer, cervical cancer, and prostate cancer . Noncoding RNA affects proliferation and differentiation, cell senescence by affecting the level of autophagy in embryos or cancer .…”