Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

Xuehui Wang,Wenfang Zheng,Changle Ji,Yunhe Yu,Lin Fang,Jiashu Hu,Xiqian Zhou,Xiaochong Deng,Kaiyao Hua

doi:10.1186/s13046-021-01830-z

Abstract

BackgroundCircular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC.MethodsThe expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1.ResultsHsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression.ConclusionsHsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

Highlights

Circular RNAs, a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC)
The characteristic of hsa_circ_0005273 in BC cells GSE113230 was a dataset of non-coding RNA profiling by high throughput sequencing in triple negative BC
To validate the existence of hsa_circ_0005273 in BC cells, we examined the PCR products amplified by primers on 1% agarose gel

Summary

Introduction

Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. The potential functional role of hsa_circ_0005273 in BC remains largely unknown. We aim to evaluate the role of hsa_circ_0005273 in BC. Circular RNAs (circRNAs), a novel class of endogenous non-coding RNAs (ncRNAs), are formed from exons or introns through special selective shearing [3]. Aberrant expression of circRNAs are correlated with the progression and prognosis of various cancers [11]. Emerging evidence illustrated that circRNAs play key oncogenic or anti-cancer roles in multiple cancers, including BC. CircRNA_0025202 regulates tamoxifen sensitivity and tumor progression via regulating FOXO3a [12]. The potential function and molecular mechanisms of circRNAs in BC need further investigation

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