miR-132 Regulates Adriamycin Resistance in Colorectal Cancer Cells Through Targeting Extracellular Signal-Regulated Kinase 1.

Abstract

Objective: Extracellular signal-regulated kinase 1 (ERK1) is an important signal transduction molecule in the ERK/mitogen-activated protein kinase pathway. miR-132 downregulation is associated with colorectal cancer (CRC). However, whether it is related to drug resistance remains poorly understood. Bioinformatics analysis demonstrated the targeting relationship between miR-132 and ERK1 3'-UTR. This study investigated the role of miR-132 in regulating ERK1 expression and affecting CRC cell proliferation, apoptosis, and adriamycin (ADM) resistance. Materials and Methods: Dual luciferase reporter gene assay was used to evaluate the targeted relationship between miR-132 and ERK1. ADM-resistant cell lines Lovo/ADM and SW480/ADM were established followed by analysis of miR-132 and ERK1 expression levels, and cell proliferation by cell counting kit-8 assay. The impact of ADM on cell proliferation and apoptosis was assessed by 5-bromodeoxyuridine (EdU) staining and flow cytometry, respectively. Lovo/ADM and SW480/ADM cells were cultured in vitro and divided into two groups, including miR-NC group and miR-132 mimic group. Results: There was a targeted regulatory relationship between miR-132 and ERK1 mRNA. The miR-132 expression was significantly lower, whereas ERK1 mRNA and protein expression levels were significantly higher in Lovo/ADM and SW480/ADM cells than those in Lovo and SW480 cells. Transfection of miR-132 mimic significantly reduced the expression of ERK1 in Lovo/ADM and SW480/ADM cells, enhanced cell apoptosis, and weakened cell proliferation. Conclusions: miR-132 reduction and ERK1 elevation are related to ADM resistance in CRC cells. Upregulation of miR-132 expression inhibits CRC cell proliferation, induces apoptosis, and reduces ADM resistance possibly by targeting ERK1 expression.

• Authors: Yong Liu, Mei Zhang
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 34 Issue 6 Pg. 398-404 (Aug 2019) ISSN: 1557-8852 [Electronic] United States
• PMID: 30939040 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• Antibiotics, Antineoplastic
• MIRN132 microRNA, human
• MicroRNAs
• Doxorubicin
• MAPK3 protein, human
• Mitogen-Activated Protein Kinase 3

Topics

• Antibiotics, Antineoplastic (pharmacology)
• Apoptosis
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (drug therapy, genetics, metabolism, pathology)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MicroRNAs (genetics)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured