Background Breast cancer remains the most common malignancy in females around the world. Recently, a growing number of studies have focused on gene dysregulation. In our previous study, Krüppel‐like factors (KLFs) were found to play essential roles in breast cancer development, among which KLF2 could function as a tumor suppressor. Nevertheless, the underlying molecular mechanism remains unclear. Methods miR‐92a‐3p was identified as the upstream regulator of KLF2 by starBase v.3.0. The regulation of KLF2 by miR‐92a‐3p was verified by a series of in vitro and in vivo assays. Further exploration revealed that Baculoviral IAP Repeat Containing 5 (BIRC5) was the target of KLF2. ChIP assay, dual‐luciferase reporter analysis, quantitative real‐time PCR, and western blot were performed for verification. Results miR‐92a‐3p functioned as a tumor promoter by inhibiting KLF2 by binding to its 3'‐untranslated region (3'‐UTR). In addition, KLF2 could transcriptionally suppress the expression of BIRC5. Conclusion Collectively, our results uncovered the miR‐92a‐3p/KLF2/BIRC5 axis in breast cancer and provided a potential mechanism for breast cancer development, which may serve as promising strategies for breast cancer therapy.

Background Breast cancer is the major cause of death in females globally. Chemokine-like factor like MARVEL transmembrane domain containing 7 (CMTM7) is reported as a tumor suppressor and is involved in epidermal growth factor receptor degradation and PI3K/AKT signaling in previous studies. However, other molecular mechanisms of CMTM7 remain unclear. Methods The expression level of CMTM7 in breast cancer cells and tissues was detected by qRT-PCR and western blot, and the methylation of CMTM7 promoter was detected by BSP sequencing. The effect of CMTM7 was verified both in vitro and in vivo, including MTT, colony formation, EdU assay, transwell assay and wound healing assay. The interaction between CMTM7 and CTNNA1 was investigated by co-IP assay. The regulation of miR-182-5p on CMTM7 and TCF3 on miR-182-5p was detected by luciferase reporter assay and ChIP analysis. Results This study detected the hypermethylation levels of the CMTM7 promoter region in breast cancer tissues and cell lines. CMTM7 was performed as a tumor suppressor both in vitro and in vivo. Furthermore, CMTM7 was a direct miR-182-5p target. Besides, we found that CMTM7 could interact with Catenin Alpha 1 (CTNNA1) and regulate Wnt/β-catenin signaling. Finally, transcription factor 3 (TCF3) can regulate miR-182-5p. We identified a feedback loop with the composition of miR-182-5p, CMTM7, CTNNA1, CTNNB1 (β-catenin), and TCF3, which play essential roles in breast cancer progression. Conclusion These findings reveal the emerging character of CMTM7 in Wnt/β-catenin signaling and bring new sights of gene interaction. CMTM7 and other elements in the feedback loop may serve as emerging targets for breast cancer therapy.