Effect of MiR-193a-3p on Bevacizumab Resistance in Colorectal Cancer via the PTEN/AKT Pathway

Liping Feng, Xianghui Liao

Article ID: 7115
Vol 37, Issue 1, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.9
Received: 8 February 2023; Accepted: 8 February 2023; Available online: 8 February 2023; Issue release: 8 February 2023

Abstract

Aims: Colon cancer (CRC) is one of the common malignant tumors of digestive tract, and the main purpose of this study is to study the effect of miR-193a-3p and its probable pathway in the regulating of bevacizumab resistance in CRC. Methods: A bevacizumab-resistant CRC xenograft mice model was established by injecting LoVo cells. The miR-193a-3p mRNA level was determined by RT-PCR (Reverse Transcription-Polymerase Chain Reaction). The CCK-8 (Cell Counting Kit-8) assay and colony formation assay were respectively used to estimate cell viability and proliferation. The wound healing and Transwell assay were used to measure the migration and invasion of cells, respectively. Epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, and Vimentin), PTEN (Phosphatase and tensin homolog deleted on chromosome ten), p-AKT (protein kinase B), AKT, p-mTOR (p-mammalian/mechanistic target of rapamycin) and mTOR levels were detected using western blot (WB) assay. The targeting relationship between miR-193a-3p and PTEN was verified by bioinformatics prediction and double luciferase reporter gene experiment. Results: MiR-193a-3p has a high expression in bevacizumab-resistant LoVo-R, and SW480-R. Silencing of miR-193a-3p suppressed the proliferation, viability, migration, and invasion of LoVo-R and SW480-R cells. Moreover, silencing of miR-193a-3p decreased the expression level of EMT. The down-regulated expression of miR-193a-3p enhanced the PTEN expression, but decreased the expression levels of p-AKT/AKT and p-mTOR/mTOR. Conclusions: MiR-193a-3p enhances bevacizumab resistance of CRC through regulating the PTEN/AKT pathway.


Keywords

miR-193a-3p;PTEN/AKT pathway;colorectal cancer;bevacizumab


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Supporting Agencies



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