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

Abstract

Background 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. 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. Methods The 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. Results Hsa_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. Conclusions Hsa_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.

Circular RNAs: Emerging Regulators of the Major Signaling Pathways Involved in Cancer Progression

“…More specifically, circRNAs can regulate the cell cycle by exerting their sponging ability; for instance, circ-ZNF292 inhibits cell proliferation and promotes apoptosis of hepatocellular carcinoma cells by regulating the WNT/β-catenin pathway [ 36 ]. An additional example is circ_0005273 (gene of origin: PTK2 ), which regulates the Hippo/YAP (YAP1) pathway through sponging miR-200a-3p, in order to promote breast cancer tumorigenesis [ 37 ]. Proteins encoded by circRNAs are implicated in signaling regulation as well.…”

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

“…A great many studies have supported that circRNA affects various diseases, like cardiovascular diseases, cancer and neurological diseases [ 6 , 7 ]. Recently, based on ever-growing studies, circRNA is crucial in treating and diagnosing BC [ 8 , 9 ]. CircCNOT2, a recently identified circRNA, is highly expressed in BC.…”

Resveratrol Inhibits Hepatic Stellate Cell Activation via the Hippo Pathway

“…Abnormalities in the Hippo pathway can result in YAP/TAZ hyperactivation, which may contribute to the occurrence and development of many human diseases, including inflammation, fibrosis, and cancer [ 14 , 32 ]. For instance, abnormal Hippo pathway activation has been observed during breast cancer tumorigenesis [ 33 ]. It has recently been reported that the Hippo/Yap pathway plays a key role in hepatic fibrogenesis [ 16 ].…”