PMID- 35706821 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2219-6803 (Electronic) IS - 2218-676X (Print) IS - 2218-676X (Linking) VI - 11 IP - 5 DP - 2022 May TI - Therapeutic potential of anti-miR29a in breast cancer patients with type 2 diabetes: an in vitro and xenograft mouse-model study. PG - 1285-1296 LID - 10.21037/tcr-22-824 [doi] AB - BACKGROUND: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM. METHODS: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated. RESULTS: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1). CONCLUSIONS: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM. CI - 2022 Translational Cancer Research. All rights reserved. FAU - Li, Zhihua AU - Li Z AD - Department of Breast Surgery, Third Hospital of Nanchang, Nanchang, China. AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Min, Liangliang AU - Min L AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Chen, Lu AU - Chen L AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Hu, Yangyang AU - Hu Y AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Luan, Wenjing AU - Luan W AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Li, Cong AU - Li C AD - Department of Breast Surgery, Third Hospital of Nanchang, Nanchang, China. AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Xiong, Qiuyun AU - Xiong Q AD - Department of Breast Surgery, Third Hospital of Nanchang, Nanchang, China. AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. FAU - Huang, Kedi AU - Huang K AD - Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China. AD - Orthopaedics Department, Third Hospital of Nanchang, Nanchang, China. LA - eng PT - Journal Article PL - China TA - Transl Cancer Res JT - Translational cancer research JID - 101585958 PMC - PMC9189168 OTO - NOTNLM OT - Anti-miR-29a OT - breast cancer OT - diabetes mellitus OT - sirtuin 1 (SIRT1) OT - target therapy COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-824/coif). The authors have no conflicts of interest to declare. EDAT- 2022/06/17 06:00 MHDA- 2022/06/17 06:01 PMCR- 2022/05/01 CRDT- 2022/06/16 02:28 PHST- 2022/03/08 00:00 [received] PHST- 2022/04/28 00:00 [accepted] PHST- 2022/06/16 02:28 [entrez] PHST- 2022/06/17 06:00 [pubmed] PHST- 2022/06/17 06:01 [medline] PHST- 2022/05/01 00:00 [pmc-release] AID - tcr-11-05-1285 [pii] AID - 10.21037/tcr-22-824 [doi] PST - ppublish SO - Transl Cancer Res. 2022 May;11(5):1285-1296. doi: 10.21037/tcr-22-824.