CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression

Weibin Shi,Shouhua Wang,Ting Ting Su,Zhiwei Quan,Huanjun Tong,Fei Ma

doi:10.1038/s41420-021-00577-y

Weibin Shi, Shouhua Wang + Show 4 more

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https://doi.org/10.1038/s41420-021-00577-y

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Abstract

Circular RNAs (circRNAs) have been implicated in modulating biological processes in some tumors. However, the contributions and molecular mechanisms of circRNAs to gallbladder cancer (GBC) remain largely unknown. In the present study, our results showed circPVT1 expression was significantly upregulated in GBC tissues and cells. Higher circPVT1 expression was correlated with lymph node metastasis, advanced TNM stage, and poor overall survival (OS) in patients with GBC. Subsequently, knockdown of circPVT1 significantly impeded GBC cell proliferation, migration, invasion, while induced cell apoptosis in vitro. However, upregulated circPVT1 had the opposite effects. In vivo, we also demonstrated that knockdown of circPVT1 inhibited tumor growth. Furthermore, we confirmed that circPVT1 could regulate Myeloid cell leukemia-1 (MCL-1) expression by sponging to miR-339-3p, which affected tumor progression in GBC cells. In summary, our findings indicated that circPVT1 may serve as a promising prognostic marker and therapeutic target for GBC.

Highlights

Gallbladder cancer (GBC) represents the most common and aggressive malignancy of all biliary tract cancer [1]
CircPVT1 is significantly upregulated in GBC and increased circPVT1 expression predicts poor prognosis in patients with GBC First, we examined the expression level of circPVT1 in 36 cases of GBC tissues and adjacent normal tissues by using quantitative realtime PCR (qRT-PCR) analysis
The results observed that the expression level of circPVT1 was significantly upregulated in GBC tissues than that in adjacent

Summary

Introduction

Gallbladder cancer (GBC) represents the most common and aggressive malignancy of all biliary tract cancer [1]. Due to the aggressive tumor biology and lack of sensitive screening tests at early stage, resulting in most of GBC patients are late presentation and intermediate to advanced stages at diagnosis [2]. Following the rapid advance of RNA sequencing technologies and bioinformatics, the novel circRNAs are recognized and some of them are involved in tumor initiation and development [6]. CircRNAs are found to participate in biological functions including cell proliferation, cell migration, cell invasion, metabolic reprogramming, and tumor metastasis [7]. Such as, circRNAs are identified as functions and properties of novel potential biomarkers for cancer [8]. In spite of the unremitting efforts of scholars, the key molecular mechanism of circRNAs involved in GBC development remains inconclusive

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