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Overexpressed methyltransferase-like 1 (METTL1) increased chemosensitivity of colon cancer cells to cisplatin by regulating miR-149-3p/S100A4/p53 axis
- Source :
- Aging (Albany NY)
- Publication Year :
- 2019
- Publisher :
- Impact Journals, LLC, 2019.
-
Abstract
- Methyltransferase-like 1 (METTL1) mediated 7-methylguanosine (m7G) is crucial for the regulation of chemoresistance in cancer treatment. However, the role of METTL1 in regulating chemoresistance of colon cancer (CC) cells to cisplatin is still unclear. This study established the cisplatin-resistant CC (CR-CC) cells and found that METTL1 was low-expressed in CR-CC cells compared to their paired cisplatin-sensitive CC (CS-CC) cells. Besides, overexpressed METTL1 enhanced the cytotoxic effects of cisplatin on CR-CC cells. In addition, miR-149-3p was the downstream target of METTL1, which could be positively regulated by METTL1. Further results validated that miR-149-3p was low-expressed in CR-CC cells comparing to the CS-CC cells. In addition, the promoting effects of overexpressed METTL1 on cisplatin induced CR-CC cell death were abrogated by synergistically knocking down miR-149-3p. Furthermore, S100A4/p53 axis was the downstream target of METTL1 and miR-149-3p, and either overexpressed METTL1 or miR-149-3p increased p53 protein levels in CR-CC cells, which were reversed by upregulating S100A4. Similarly, the promoting effects of overexpressed METTL1 on cisplatin-induced CR-CC cell death were abrogated by overexpressing S100A4. Taken together, overexpression of METTL1 sensitized CR-CC cells to cisplatin by modulating miR-149-3p/S100A4/p53 axis.
- Subjects :
- Aging
Programmed cell death
Methyltransferase
Colorectal cancer
cisplatin
Antineoplastic Agents
Gene Expression Regulation, Enzymologic
Cell Line, Tumor
medicine
Humans
S100A4
Cytotoxic T cell
S100 Calcium-Binding Protein A4
Cisplatin
Chemistry
Methyltransferases
Cell Biology
miR-149-3p
medicine.disease
Cancer treatment
Gene Expression Regulation, Neoplastic
MicroRNAs
colon cancer
Drug Resistance, Neoplasm
Colonic Neoplasms
METTL1
P53 protein
Cancer research
Tumor Suppressor Protein p53
Research Paper
medicine.drug
Subjects
Details
- ISSN :
- 19454589
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Aging
- Accession number :
- edsair.doi.dedup.....d12ac927c0141b052badfadcf32a4c7a