miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway

Abstract

MicroRNAs (miRs/miRNAs) play important roles in the occurrence, metastasis and prognosis of multiple types of cancers. However, the specific role of miR-302d-3p and its underlying mechanism in breast cancer (BC) have not yet been reported. The present study aimed to identify the role of miR-302D-3p in BC and its potential mechanism using BC cell lines MCF7 and MDA-MB-231 and normal breast epithelial cell MCF-10A. Cancer and paracancerous tissue from patients with BC were also used. Reverse transcription-quantitative PCR was performed to detect the expression of miR-302d-3p and transmembrane Bax inhibitor motif containing 6 (TMBIM6). Dual-luciferase reporter assays verified the binding sites of miR-302d-3p and TMBIM6. Immunohistochemistry was used to measure the expression of TMBIM6. Cell transfection techniques were used to overexpress or interfere with miR-302d-3p and TMBIM6. A Cell Counting Kit-8 assay was performed to detect cell viability, and migration was measured using a wound healing assay. Apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins and pathway-related proteins were detected by western blotting. The expression of miR-302d-3p in BC cell lines was found to be downregulated. It was also demonstrated that miR-302d-3p could inhibit cell viability and migration and promote apoptosis. The expression of TMBIM6 in BC cell lines and tissues was upregulated. Upregulated miR-302d-3p was shown to inhibit viability and migration, and promote apoptosis by targeting TMBIM6, during which extracellular signal-regulated kinase (ERK) and its phosphorylation were inhibited in the ERK signaling pathway in cells. Overall, the present study demonstrated that miR-302d-3p could regulate the viability, migration and apoptosis of BC cells through regulating TMBIM6-mediated ERK signaling pathway.

RETRACTED: Exosomes From Cancer-Associated Mesenchymal Stem Cells Transmit TMBIM6 to Promote the Malignant Behavior of Hepatocellular Carcinoma via Activating PI3K/AKT Pathway

“…In cancers, TMBIM6 is regarded as a promoter of cancer progression. For example, TMBIM6 regulates the extracellular signal-regulated kinase (ERK) pathway to promote the proliferation and migration of breast cancer cells ( 46 ). Another study reveals that TMBIM6 enhances proliferation and metastasis in non-small cell lung cancer cells ( 47 ).…”

Characteristics and significance of programmed cell death‐related gene expression signature in skin cutaneous melanoma

“…40 Furthermore, miR-302d-3p-mediated regulation of TMBIM6 has been implicated in breast cancer cell viability, migration, and apoptosis, highlighting the potential therapeutic implications of targeting TMBIM6 and its associated downstream signaling pathways. 41 These findings collectively underscore the significance of TMBIM6 in cancer progression and advocate for its potential util- Targeting immune pathways associated with the recruitment and functionality of macrophages may represent a compelling therapeutic approach for improving outcomes in SKCM patients. Tumor-associated macrophages (TAMs) have emerged as a promising therapeutic target in the management of melanoma.…”

STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent

“…TMBIM6, also named as transmembrane Bax inhibitor motif containing-6, is an inhibitor of Bax-induced apoptosis [48]. Growing evidences has indicated that TMBIM6 exert an oncogenic role in multiple cancers, including squamous cervical, non-small cell lung, breast, nasopharyngeal, hepatocellular, glioblastoma, and laryngeal squamous cell carcinoma [29,37,45,[49][50][51][52][53]. Our study implied that TMBIM6 was modified by m6A in the transcription level and interacts with IGF2BP3 and STRIP2, resulting in the stabilization of TMBIM6.…”