CircCEMIP promotes anoikis-resistance by enhancing protective autophagy in prostate cancer cells

Abstract

Background Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis. Methods This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays. Results Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation. Conclusions These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.

A Bioinformatics-Based Analysis of an Anoikis-Related Gene Signature Predicts the Prognosis of Patients with Low-Grade Gliomas

“…Tumor cells have been found to resist anoikis in a variety of ways, such as secreting growth factors, activating pro-survival signaling pathways, or altering the expression pattern of integrins by cells [ 11 ]. Resistance to anoikis is becoming a hallmark of cancer cells and contributes to the formation of distant organ metastases [ 12 , 13 ]. However, few studies focused on the relationship between the process of anoikis and distant metastasis of LGGs.…”

A novel anoikis-related gene signature predicts prognosis in patients with head and neck squamous cell carcinoma and reveals immune infiltration

“…Normally, when normal epithelial cells detach, they lose critical survival factors and undergo a programmed cell death called anoikis (Nirmala and Lopus, 2020), while HNSCC metastatic tumor cells gain anoikis resistance, which allows them to begin curating away from the primary lesion (Braunholz et al, 2016;Liao et al, 2017;Shen et al, 2017). Owing of the fact that anchorage-dependent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are critical steps in tumor progression and metastatic spread of cancer cells, anoikis dysregulation is now of particular interest to the scientific community (Talukdar et al, 2018;Corbet et al, 2020;Ye et al, 2020;Yoon and DeNicola, 2021;Yu et al, 2022). Multiple pathways can lead to the acquisition of anoikis resistance in HNSCC (Dey et al, 2015), and these highlight the concept of targeting anoikis-related genes to overcome HNSCC progression and metastasis (Kumar et al, 2010).…”

“…Anoikis is a form of programmed cell death, which is essential for the survival of tumor cells after detachment from the extracellular matrix (ECM) (Xiao et al, 2019;Zhou et al, 2022). The generation of anoikis resistance in aggressive tumor cells has been identified as a key factor in tumor progression (Berezovskaya et al, 2005;Kim et al, 2012;Yu et al, 2022). However, few studies have focused on the association between the anoikis process and distant metastasis of HNSCC.…”

Circular RNA-regulated autophagy is involved in cancer progression

“…miR-520h could be bound by circCSPP1 and affect the EGR1 expression to mediate the abovementioned effects. Yu et al (2022) identified highly expressed circCEMIP in PCA cells and tissues, which functioned as a miR-1248 sponge to regulate downstream TM9SF4 protein expression level, further inhibiting mTOR phosphorylation and facilitating the autophagy process. Following experiments indicated that enhanced autophagy protected PCA cells from anoikis, accelerating PCA progression.…”