» Articles » PMID: 33198772

Circular RNA MCTP2 Inhibits Cisplatin Resistance in Gastric Cancer by MiR-99a-5p-mediated Induction of MTMR3 Expression

Overview
Publisher Biomed Central
Specialty Oncology
Date 2020 Nov 17
PMID 33198772
Citations 52
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated.

Methods: RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).

Results: CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model.

Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.

Citing Articles

Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Lu L, Gao Z, Jin L, Geng H, Liang Z Front Pharmacol. 2024; 15:1435264.

PMID: 39314750 PMC: 11416928. DOI: 10.3389/fphar.2024.1435264.


Circular RNA circRNA_100349 functions as a miR-218-5p sponge for suppressing the cell proliferation of gastric cancer via regulation of IGF2 expression.

Lin L, Wusiman J, Zhang Z Clinics (Sao Paulo). 2024; 79:100492.

PMID: 39293372 PMC: 11422554. DOI: 10.1016/j.clinsp.2024.100492.


Biologic activity and treatment resistance to gastrointestinal cancer: the role of circular RNA in autophagy regulation.

Zhang B, Li Z, Ye G, Hu K Front Oncol. 2024; 14:1393670.

PMID: 39281375 PMC: 11392687. DOI: 10.3389/fonc.2024.1393670.


The multifaceted roles of circular RNAs in cancer hallmarks: From mechanisms to clinical implications.

Kundu I, Varshney S, Karnati S, Naidu S Mol Ther Nucleic Acids. 2024; 35(3):102286.

PMID: 39188305 PMC: 11345389. DOI: 10.1016/j.omtn.2024.102286.


Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective.

Wang T, He M, Zhang X, Guo Z, Wang P, Long F Cell Mol Biol Lett. 2024; 29(1):60.

PMID: 38671354 PMC: 11046940. DOI: 10.1186/s11658-024-00571-z.


References
1.
Zhang C, Zhang C, Ma M, Dai D . Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients. World J Gastroenterol. 2018; 24(11):1206-1215. PMC: 5859223. DOI: 10.3748/wjg.v24.i11.1206. View

2.
Catalano V, Labianca R, Beretta G, Gatta G, De Braud F, Van Cutsem E . Gastric cancer. Crit Rev Oncol Hematol. 2009; 71(2):127-64. DOI: 10.1016/j.critrevonc.2009.01.004. View

3.
Katheder N, Khezri R, OFarrell F, Schultz S, Jain A, Rahman M . Microenvironmental autophagy promotes tumour growth. Nature. 2017; 541(7637):417-420. PMC: 5612666. DOI: 10.1038/nature20815. View

4.
Mizushima N, Komatsu M . Autophagy: renovation of cells and tissues. Cell. 2011; 147(4):728-41. DOI: 10.1016/j.cell.2011.10.026. View

5.
Aktas T, Ilik I, Maticzka D, Bhardwaj V, Pessoa Rodrigues C, Mittler G . DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome. Nature. 2017; 544(7648):115-119. DOI: 10.1038/nature21715. View