CMTM7 inhibits breast cancer progression by regulating Wnt/β-catenin signaling

Abstract

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.

Berberine inhibits the progression of breast cancer by regulating METTL3‐mediated m6A modification of FGF7 mRNA

“…As expected, our data verified that METTL3 upregulation might partly abrogate BBR‐mediated FGF7 reduction in breast cancer cells, further supporting the regulatory mechanism of BBR/METTL3/FGF7 in breast cancer. In addition, previous studies have indicated that aberrant activation of the Wnt/β‐catenin signaling pathway is one of the main reasons for breast tumorigenesis and metastasis 43,44 . Meanwhile, it has been reported that BBR might suppress tumor growth in various human cancers by repressing Wnt/β‐catenin signaling, 45,46 containing breast cancer 47 .…”

“…In addition, previous studies have indicated that aberrant activation of the Wnt/β‐catenin signaling pathway is one of the main reasons for breast tumorigenesis and metastasis. 43 , 44 Meanwhile, it has been reported that BBR might suppress tumor growth in various human cancers by repressing Wnt/β‐catenin signaling, 45 , 46 containing breast cancer. 47 Furthermore, FGF7 might induce the accumulation of cytoplasmic β‐catenin.…”

Enhancing the Anti-Tumor Efficacy of NK Cells on Canine Mammary Tumors through Resveratrol Activation

“…This process is characterized by a loss of the epithelial marker E-cadherin, along with increased expression of the mesenchymal markers Vimentin and N-cadherin [ 27 , 28 , 29 ]. Recent studies have highlighted the impact of the EMT process on the anti-tumor efficacy of NK cells, particularly emphasizing the role of E-cadherin expression in NK cell-mediated cytotoxicity [ 30 ] Additionally, the Wnt/β-catenin signaling pathway is known to be significantly activated in highly invasive metastatic breast tumor cell lines, with an overactive pathway correlating with poor clinical prognosis [ 31 , 32 , 33 , 34 ]. In light of this, the current study investigated the expression of EMT and Wnt/β-catenin pathway-related proteins in CHMm cells following co-incubation with NK cells.…”

PAX5-miR-142 feedback loop promotes breast cancer proliferation by regulating DNMT1 and ZEB1

“…Other miRNAs such as miR-296 and miR-130a are also associated with tumor angiogenesis through interaction with pro-angiogenic receptors and antiangiogenic factors such as HGS, HOXA5, and GAX, respectively (Wurdinger et al 2008 ; Chen and Gorski 2008 ). While in breast cancer, miR-182-5p was reported as a tumor promoter and involved in breast cancer progression by targeting CMTM7 in our previous study (Chen et al 2023 ).miR-142-5p and miR-142-3p are two single-stranded miRNAs derived from the same RNA duplex and were first reported by Wu et al in 2007 (Wu et al 2007 ).miR-142-5p and miR-142-3p are both reported to play essential roles in cancer initiation and progression (Pahlavan et al 2020 ). Chenfei Zhou et al reported that miR-142-5p that derived from exosome could promote immune privilege by IDO in the tumor microenvironment (Zhou et al 2021 ).…”