Down-regulation of miR-29a facilitates apoptosis of colorectal carcinoma cell SW480 and suppresses its Paclitaxel resistance
Authors: C-J Lei
L-L Yuan
L Li
J Mei
J-N Liu
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PTEN; miR-29a; Paclitaxel sensitivity; colorectal carcinoma cells; drug resistance
Affiliations: Department of Anesthesiology, the Fifth Hospital of Wuhan, Wuhan, Hubei, China. .

Abstract:  Objective: PTEN can suppress PI3K/AKT activity, and regulate cell proliferation, apoptosis, and drug resistance. The previous study showed that up-regulation of miR-29a played an essential role in the occurrence of colorectal carcinoma. This study aimed to investigate the role and related mechanism of miR-29a in mediating Paclitaxel sensitivity of colorectal carcinoma cells. Materials and methods: Bioinformatics analysis was performed to study the existence of binding sites between miR-29a and targeting gene mRNA. Dual luciferase reporter assay was conducted to validate the targeted regulation. The expressions were compared between CCD841 CoN cells, colorectal carcinoma cell line SW480, and drug-resistant cell line SW480/Paclitaxel. Cell apoptosis and proliferation were measured by flow cytometry. In vitro cultured SW480/Paclitaxel cells were transfected with miR-29a or pcDNA3.1-PTEN. MiR-29a and PTEN expressions were measured by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blot, followed by flow cytometry on the detection of cell apoptosis as well as proliferation assay. Results: A targeted regulatory relationship existed between miR-29a and PTEN. Comparing to CCD841 CoN cells, high level of miR-29a and decreasing expression of PTEN were found in SW480 cells. Moreover, further higher miR-29a and lower PTEN expressions were observed in SW480/Paclitaxel cells. Paclitaxel remarkably inhibited proliferation and facilitated apoptosis of SW480 cells but not SW480/Paclitaxel cells. Transfection of miR-29a inhibitor or pcDNA3.1-PTEN remarkably elevated PTEN expression, suppressed p-AKT expression, weakened proliferation, and enhanced apoptosis of SW480/Paclitaxel cells. Conclusions: Our data demonstrated that suppression of miR-29a enhanced PTEN expression, inhibited cancer cell proliferation, facilitated apoptosis, and weakened drug resistance, which provides academic basis for the treatment of colorectal cancer. 

Retracted: No

PubPeer comments:
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