miR-3614–5p downregulation promotes cadmium-induced breast cancer cell proliferation and metastasis by targeting TXNRD1

• Published in: Ecotoxicology and environmental safety Vol. 247; p. 114270
• Main Authors: Yue, Yang, Tan, Miduo, Luo, Yan, Deng, Ping, Wang, Hui, Li, Jingdian, Hao, Rongrong, Tian, Li, Xie, Jia, Chen, Mengyan, Yu, Zhengping, Zhou, Zhou, Pi, Huifeng
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-12-2022; Elsevier
• Subjects: Breast cancer; Cadmium; MiR-3614–5p; TXNRD1; PTGER4; BC; Cd; RASGRF2; PLD5; PLD1; siRNAs; GRM3; RELN; KEGG; miRNA; NOS1; RNF150; GRIA3; MiR-3614–5p; SLC17A4; Cadmium; NSCLC; TXNRD1; 3′-UTR; HCC; Breast cancer; ALDH1A3; TG; NGS; FBN1
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.114270

Cadmium (Cd), which is considered an endocrine disruptor, has been linked to the onset of breast cancer (BC). Our recent study demonstrated that Cd-induced BC progression has a strong correlation with miR-374c-5p dysregulation. The aim of our work was to investigate other potential miRNAs involved in Cd-induced BC cell proliferation and metastasis. In our study, the miRNA profiles of Cd-treated T-47D cells (10 μM, 72 h) were analyzed by miRNA-seq, and our results confirmed that miR-3614–5p was the top downregulated miRNA. Moreover, miR-3614–5p mimic transfection significantly decreased the proliferative ability, migration and invasive ability of BC cell lines (T-47D and MCF-7). Furthermore, we analyzed the overlapping genes from our RNA-seq data and predicted targets from the mirDIP database, and twelve genes (ALDH1A3, FBN1, GRIA3, NOS1, PLD5, PTGER4, RASGRF2, RELN, RNF150, SLC17A4, TG, and TXNRD1) were identified as potential binding targets of miR-3614–5p in the current model. Nonetheless, only miR-3614–5p inhibition caused an increase in TXNRD1 expression upon Cd exposure in T-47D and MCF-7 cell lines. Importantly, luciferase reporter assays further verified that miR-3614–5p suppressed the expression of TXNRD1 by directly binding to the 3′-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614–5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.
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•miR-3614–5p is ranked as the TOP1 down-regulated miRNA in Cd-treated BC cells.•Cd enhances breast cancer progression by inhibiting miR-3614–5p.•TXNRD1 serves as a hub gene in Cd-enhanced breast cancer progression.•miR-3614–5p downregulation promotes Cd-induced breast cancer progression by increasing TXNRD1.