Circular RNA 000554 represses epithelial‐mesenchymal transition in breast cancer by regulating microRNA‐182/ZFP36 axis

Abstract

Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR‐182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR‐182 expression were determined in the clinical BC tissues. CircRNA_000554 acted as a sponge of miR‐182, and miR‐182 directly targeted ZFP36. After that, in order to evaluate the effects of circRNA_000554, miR‐182, and ZFP36 on cellular process, we evaluated in vitro epithelial‐mesenchymal transition (EMT) and in vivo tumor growth after delivering a series of overexpression plasmids, mimic, inhibitor, or shRNAs into BC cells. Increasing circRNA_000554 suppressed EMT, cell invasion and migration during BC by depleting miR‐182 and increasing ZFP36. The inhibitory effect of circRNA_000554 on tumor growth was validated in vivo. Taken together, the present study confirms that circRNA_000554 functioned as an inhibitor of EMT in BC and suggests a molecular mechanism that circRNA_000554 bound to miR‐182 to upregulate ZFP36 in this process.

Prognostic significance of circRNAs expression in breast carcinoma patients: A meta-analysis

“…Cut-off values of high or low circRNA expression were mostly median or mean.The range of mean duration of follow□up was from 30 to 250 months.Moreover,Detection methods of circRNA expression were mainly quantitative real□time polymerase chain reaction (RT□PCR).Sample types were almost from tissues. As for clinical outcome indicators, 27 studies[10, 11, 13-34],[35-37]included overall survival (OS), 5 studies[19, 29, 31, 33, 38]included disease-free survival (DFS).As shown in Table 3, nineteen types of circRNAs were recognized as tumor promoters and nine were tumor suppressors. 28 circrnas have corresponding targets and can promote or inhibit the proliferation, invasion and metastasis of breast cancer cells.…”

“…In addition, the upregulation of CIRc_0103552 can also promote cell growth, clonal formation, migration and invasion, and reduce apoptotic cells. A recent study [11]showed that the expression of circRNA_000554 in BC tissues was significantly lower than that in normal tissues, and the survival time of hsa_circRNA_000554 with low expression was shorter than that of circRNA_000554 with overexpression. In addition, they found that circRNA_000554 with overexpression inhibited EMT, cell invasion and migration during breast cancer by decreasing Mir-182 and increasing ZFP36.…”

The Regulation Network and Clinical Significance of Circular RNAs in Breast Cancer

“…Both CircRNAs 000554 and circRNA_0025202 can sponge miR-182 to regulate the expression of ZNF36 and FOXO3a, respectively, and thus inhibit cellular proliferation, invasion, migration, and sensitivity to chemotherapy agents (155,156). Similarly, circRNA-0001283 functions to sponge miR-187 to suppress HIPK3 expression, thus inhibiting the proliferation and invasion and promoting the apoptosis of breast cancer cells (157).…”

Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis

“…miRNAs, a class of non-coding RNA approximately 22 nt in length, exert crucial roles in the initiation and progression of cancer, acting either as oncomiRs or as tumor suppressors through several molecular mechanisms (Markopoulos 2017 ). miR-182 inhibition contributes to suppressed epithelial-mesenchymal transition, invasion and migration of breast cancer cells in vitro along with tumor growth in vivo (Mao 2020 ). TargetScan website predicted the binding sites between miR-182-5p and CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7), a member of the CMTM family playing key roles in the occurrence and progression of cancer.…”