Circ-TRIO promotes TNBC progression by regulating the miR-432-5p/CCDC58 axis

Abstract

Numerous studies have shown that circRNAs are aberrantly expressed in various cancers and play a significant role in tumor progression. However, the molecular mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain ambiguous. By intersecting throughput data and qRT-PCR results from tissues and cell lines, circ-TRIO was identified as a potential oncogenic regulator of TNBC. Moreover, circ-TRIO expression was detected in TNBC tissues and was correlated with the recurrence and prognosis of TNBC patients. The circular characteristics of circ-TRIO were verified by RNase R and CHX assays. Functionally, the knockdown of circ-TRIO inhibited the proliferation, migration and invasion of TNBC cells, while the overexpression of circ-TRIO resulted in the opposite impacts. Mechanistically, a dual luciferase reporter assay and RNA immunoprecipitation were performed and indicated that circ-TRIO could combine with miR-432-5p to regulate the expression of coiled-coil domain containing 58 (CCDC58). In summary, our study illustrates that circ-TRIO plays an important role in the progression of TNBC by regulating the miR-432-5p/CCDC58 axis, which could broaden our insight into the underlying mechanisms and provide a novel prognostic marker of TNBC in the clinic.

A pan-cancer analysis has uncovered CCDC58, a mitochondrial gene associated with epilepsy, as a potential prognostic and immunotherapeutic biomarker for various cancer types, including gliomas

“…The process of e cient protein import into the mitochondrial matrix is regulated or stabilized by CCDC58 (34). By controlling the miR-432-5p/CCDC58 axis, Circ-TRIO has been found to affect the ability of tumor cells to proliferate and migrate in triple-negative breast cancer (TNBC) (14). Reportedly, elevated levels of CCDC58 are also predictive of a poor prognosis in hepatocellular carcinoma (35).…”

“…In the context of epilepsy, mitochondrial disorders impact oxidative stress, disrupted calcium homeostasis, immune function, and the modi cation of vitamins, cofactors, reducing equivalents, and other metabolites, consequently in uencing neuronal excitability and susceptibility to epilepsy (12). CCDC58 (coiled-coil domain containing 58), also known as MIX23 (mitochondrial matrix import Factor 23), is abundant in human and mouse brain, bone, and heart tissues, and it is predominantly located within mitochondria (13)(14)(15). The study demonstrates that Mix23 serves as a novel regulator or stabilizer of the mitochondrial protein import machinery, particularly up-regulated under conditions of mitoprotein-induced stress(16).…”

“…The study demonstrates that Mix23 serves as a novel regulator or stabilizer of the mitochondrial protein import machinery, particularly up-regulated under conditions of mitoprotein-induced stress(16). The elevated level of CCDC58 suggests a dismal prognosis for hepatocellular carcinoma, uroepithelial carcinoma, and triple-negative breast cancer (14). However, the function of CCDC58 in other cancers, especially gliomas, has not been con rmed.…”

CircRNA_0044556 regulates paclitaxel resistance in triple-negative breast cancer by targeting miR-665

“…Therefore, acquired resistance to paclitaxel is undoubtedly the biggest obstacle in improving the overall response and survival of patients with TNBC. In recent years, owing to the stability and abundance of circRNAs, an increasing number of circRNAs have been identi ed as abnormally expressed in TNBC; as important regulators of TNBC cancer progression, circRNAs are of great signi cance for the resistance of TNBC [9,19]. However, research on circRNAs associated with paclitaxel resistance in TNBC remains limited.…”

Myc derived circRNA promotes triple-negative breast cancer progression via reprogramming fatty acid metabolism

“…Recent evidence suggests that circRNA has multiple modes of action, including regulation of transcription, splicing and chromatin interactions, acting as a microRNA decoy and protein scaffold, and even directly translating into functional peptides [ 9 ]. Data from us and other laboratories reveal the intrinsic linking between circRNA and breast cancer [ 10 ], for example, circBGN was upregulated in HER2-positive breast cancer and conferred trastuzumab resistance through repressing SLC7A11-mediated ferroptosis [ 11 ]; circTRIO was identified as a potential oncogenic regulator in TNBC, which regulated the miR-432-5p/CCDC58 axis [ 12 ]. Although a small number of circRNAs have been found to be associated with TNBC, a large proportion of their functions are unknown and need further elucidation.…”