LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway

Wenchan Hsu,Lifen Liu,Xin Chen,Weipei Zhu,Ying Zhang

doi:10.1186/s40659-019-0240-9

Abstract

BackgroundStudies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression.MaterialsQuantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/β-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation.ResultsWe discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients’ survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell’s proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/β-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo.ConclusionOur study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/β-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.

Highlights

Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long noncoding RNA, was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer
We discovered that CASC11, the expression of which was positively associated with the tumor size and the Federation of Gynecology and Obstetrics (FIGO) staging and negatively related to the patients’ survival rate, was up-regulated in the cervical cancer tissues and cell lines
Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/β-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo

Summary

Introduction

Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long noncoding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. Cervical cancer is one of the most common malignant tumors in women worldwide with high morbidity and mortality. Numbers of factors, such as genetic influences and viral infection, are involved in this complex disease. LncRNA is a class of single-stranded RNAs with a length of more than 200 nucleotides (nt) and without the capacity of coding proteins. It works in cell growth, survival, migration, invasion, differentiation, and other cellular processes. More than a dozen of lncRNAs including HOX transcript antisense RNA (HOTAIR), metastasis associated lung adenocarcinoma transcript 1 (MALAT1), colon cancer-associated transcript 2 (CCAT2) and so on, are involved in cervical cancer by interacting with proteins, miRNAs and other molecules, providing accurate targets for the treatment of cervical cancer patients [7]

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