Decreased expression of miR‑3135b reduces sensitivity to 5‑fluorouracil in colorectal cancer by direct repression of PIM1

Wang,Yan; Cui,Xiaofeng; Ma,Shurong; Zhang,Haishan

doi:10.3892/etm.2021.10585

Decreased expression of miR‑3135b reduces sensitivity to 5‑fluorouracil in colorectal cancer by direct repression of PIM1

Authors:
- Yan Wang
- Xiaofeng Cui
- Shurong Ma
- Haishan Zhang
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Affiliations: Science Research Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Gastrointestinal Colorectal and Anal Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Endoscopic Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: August 10, 2021 https://doi.org/10.3892/etm.2021.10585
Article Number: 1151
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

5‑Fluorouracil (5‑FU)‑based chemotherapy is the conventional treatment approach for patients with colorectal cancer (CRC). However, de novo and acquired resistance to 5‑FU are frequently observed during treatment, which eventually lead to patients succumbing to the disease. Accumulating data have revealed an association of CRC resistance to 5‑FU with aberrant expression of microRNAs (miRs). In the present study, Cell Counting Kit‑8 was performed to measure cell viability, flow cytometry was performed to detect cell apoptosis, reverse transcription‑quantitative PCR was conducted to measure proviral integration site for Moloney murine leukemia virus 1 (PIM1) and miR‑3135b expression, western blotting was conducted to measure PIM1 expression. Microarray data analysis indicated that the level of miR‑3135b expression was decreased in patients with recurrent CRC that were treated with 5‑FU when compared with non‑recurrent cases. Overexpression of miR‑3135b increased the sensitivity of CRC cells to 5‑FU treatment. Moreover, PIM1 was identified as a target gene of miR‑3135b using bioinformatics analysis, reverse transcription‑quantitative PCR and western blotting. The direct interaction between these two targets was confirmed by luciferase reporter assays. Notably, PIM1 overexpression compensated the effect of miR‑3135b in CRC cells. Furthermore, an inverse correlation between PIM1 mRNA expression levels and miR‑3135b expression was observed in clinical samples. Therefore, the present study identified miR‑3135b as a novel regulator of 5‑FU sensitivity in CRC.

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