Inhibition of microRNA-17/20a suppresses cell proliferation in gastric cancer by modulating UBE2C expression

Abstract

microRNAs (miRNAs) are small non-coding RNAs that potentially play a critical role in carcinogenesis. Increasing evidence indicates that the miR-17/20 cluster is upregulated in numerous types of human cancers including gastric cancer which suggests that the miR-17/20 cluster may play an important role in tumorigenesis. However, its role in gastric cancer carcinogenesis remains poorly defined due to the lack of target gene information. The aim of the present study was to investigate the target genes of the miR-17/20 cluster and their role in the tumor growth of gastric cancer. We found that both miR-17 and miR-20a (miR-17/20a) target the UBE2C gene in gastric cancer cells. Luciferase assay, qRT-PCR and western blot analysis confirmed that UBE2C is a direct target of miR‑17/20a in gastric cancer cells. Our results showed that the expression of UBE2C was positively regulated by miR-17/20a at both the mRNA and protein levels. Moreover, miR-17/20a was upregulated and positively associated with UBE2C in the gastric cancer tissues when compared to the adjacent nontumor tissues. Inhibition of miR-17/20a in gastric cancer cells was statistically correlated with a decrease in cell growth. These results demonstrate that upregulation of miR-17/20a promotes gastric cancer cell growth by targeting UBE2C and inhibition of their levels is a potentially promising therapeutic strategy for gastric cancer.

UBE2C induces EMT through Wnt/β-catenin and PI3K/Akt signaling pathways by regulating phosphorylation levels of Aurora-A

“…Much effort has been spent on the study of the overexpression of UBE2C biological mechanisms in gastric cancer (29,30). This E2 protein catalyzes the ubiquitination and degradation of cyclins A and B, and acts together with the E3 ligase of the APC/C to participate in the regulation of the spindle assembly checkpoint (31).…”

Clustered miRNAs and their role in biological functions and diseases

“…miR‐545/374a, miR‐183/182, miR‐106b/25 and miR‐221/222 clusters (Zhao et al, ; Zhou et al, ; Li et al, ) all enhance cell proliferation. Conversely, miR‐1/133a, miR‐212/132, miR‐23b/27b, miR‐17/20 and miR‐302/367 clusters were downregulated in cancer, and act as inhibitors of cell proliferation (Hanieh, ; Mataki et al, ; Yang et al ., ; Zha ng et al ., ; Rice et al, ) Upregulation of oncogenic and downregulation of tumour‐suppressor miRNA clusters has been shown to upregulate expression of cyclin D2 ( CCND2 ), cyclin D1 ( CCND1) and wingless‐type MMTV integration site family, member 3A ( WNT3A) (Bonci et al, ; Di Leva et al, ; Lovat et al, ) and downregulate expression of anti‐proliferative genes such as PTEN, p21 , BIM and p27 (Wong et al, ; Zhu et al, ).…”

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

“…Numerous studies have been performed on the role and related mechanism of miRNAs in numerous different kinds of diseases (9)(10)(11)(12). miRNAs bind primarily to the 3'-untranslated region (3'UTR) of their target messenger RNAs (mRNAs) to reduce their stability and decrease the expression of target mRNAs at the post-transcriptional level (13), which play important roles in various biological processes including cell growth, proliferation, differentiation and death (14)(15)(16)(17)(18)(19). Concerning chemotherapy in various types of cancers such as breast cancer, lung adenocarcinoma, glioblastoma, and ovarian cancer, recent studies have shown that miRNAs also act in important roles (20)(21)(22)(23)(24).…”