The Effect of Metformin on the Proliferation, Apoptosis and CD133 mRNA Expression of Colon Cancer Stem Cells by Upregulation of miR 342-3p

• Main Authors: Zhang Y (Author), Chen R (Author), Deng L (Author), Shuai Z (Author), Chen M (Author)
• Format: Book
• Published: Dove Medical Press, 2021-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1177-8881
• Keywords: metformin; colon cancer stem cells; tumor suppressor-related mirnas; cd133; Therapeutics. Pharmacology; RM1-950
• Source: Drug Design, Development and Therapy, Vol Volume 15, Pp 4633-4648 (2021)

Yaqin Zhang, 1,* Ruofei Chen, 1,* Lili Deng, 2 Zongwen Shuai, 1 Mingwei Chen 2 1Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People&rsquo;s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People&rsquo;s Republic of China*These authors contributed equally to this workCorrespondence: Zongwen Shuai; Mingwei Chen Email [e-mail]; [e-mail]: To explore whether metformin (MET) can affect the biological behaviour and CD133 mRNA expression of CD133+ colon cancer stem cells (CCSCs) through miR-342-3p.Methods: The direct immunomagnetic bead method was used to select CD133+ CCSCs from the SW480 and HCT116 cell lines, and miRNA-tailing qRT-PCR was used to detect the expression changes of tumor suppressor-related miRNAs (miR-34a, miR-126, miR-143, miR-145, miR-342-3p, miR-342-5p) after MET intervention. Then, miR-342-3p with markedly significant differential expression was selected as the target miRNA. The lentiviruses LV16-hsa-miR-342-3p inhibitor and LV16-NC were used for the transfection inhibition test. CCK-8, flow cytometry, and qRT-PCR were used to detect the cell viability, apoptosis rate, and CD133 mRNA expression of CD133+ CCSCs.Results: Under the high-glucose environment, the expression of tumor suppressor-related miRNAs in CCSCs changed differently (p < 0.05), MET also had different effects on the expression of tumor suppressor-related miRNA under different glucose concentrations (p< 0.05). Among them, MET upregulates the expression of miR-342-3p in CCSCs for the first time. The results of the lentiviruses transfection inhibition test showed that after miR-342-3p was inhibited, the cell viability and apoptosis rate of CD133+ CCSCs did not change significantly compared with before inhibition (p> 0.05), but the expression of CD133 mRNA markedly increased (p< 0.05). Meanwhile, after MET intervention, the apoptosis rate and the expression of CD133 mRNA of CD133+ CCSCs was significantly increased, and the proliferation of CD133+ CCSCs was obviously inhibited (p< 0.05).Conclusion: MET upregulating the expression of miR-342-3p may not have a significant effect on the proliferation and apoptosis of CD133+ CCSCs, but it can reduce the expression of CD133 mRNA in CD133+ CCSCs.Keywords: metformin, colon cancer stem cells, tumor suppressor-related miRNAs, CD133