MiR‑1260b inhibitor enhances the chemosensitivity of colorectal cancer cells to fluorouracil by targeting PDCD4/IGF1

Zhao,Jun; Cao,Jingjie; Zhou,Lurong; Du,Yunyi; Zhang,Xiaoling; Yang,Bo; Gao,Yangjun; Wang,Yu; Ma,Ning; Yang,Wei

doi:10.3892/ol.2018.9307

MiR‑1260b inhibitor enhances the chemosensitivity of colorectal cancer cells to fluorouracil by targeting PDCD4/IGF1

Authors:
- Jun Zhao
- Jingjie Cao
- Lurong Zhou
- Yunyi Du
- Xiaoling Zhang
- Bo Yang
- Yangjun Gao
- Yu Wang
- Ning Ma
- Wei Yang
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Affiliations: Department of Oncology, The Changzhi People's Hospital, Changzhi, Shanxi 046000, P.R. China, Department of Radiotherapy, The 264th Hospital of Chinese People's Liberation Army, Taiyuan, Shanxi 030001, P.R. China, Medical Department, The Changzhi People's Hospital, Changzhi, Shanxi 046000, P.R. China
Published online on: August 14, 2018 https://doi.org/10.3892/ol.2018.9307
Pages: 5131-5139
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the most common malignant tumor type and has become resistant to 5‑fluorouracil (5‑FU) in recent decades, which is one of the most popular therapies. Recently, microRNA (miRNA or miR) has been investigated as a potential therapeutic strategy for CRC. However, there has been little investigation of the underlying mechanism of the association between expression of miRNA and chemosensitivity. The present study aimed to investigate the effect of miR‑1260b inhibitor on CRC cells, and their chemosensitivity to 5‑FU, by treating them with the miR‑1260b inhibitor. miR‑1260b inhibitor was demonstrated to significantly promote the proliferation and invasion of the CRC cell line, HCT116, and to increase the apoptotic rate. Furthermore, it was validated that programmed cell death 4 (PDCD4) was a direct target of miR‑1260b inhibitor in CRC with bioinformatics tools and a luciferase assay. Western blot analysis revealed that miR‑1260b inhibitor could significantly decrease PDCD4 expression, and downregulate the expression of phosphorylated‑Akt (p‑Akt) and phosphorylated‑extracellular‑signal‑regulated kinase (p‑ERK). In conclusion, it was confirmed that the anti‑tumor effect of the miR‑1260b inhibitor was conducted by blocking the phosphorylated 3‑kinase/Akt pathway as dysregulated protein expression induced by miR‑1260b inhibitor was rescued by insulin‑like growth factor. Notably, miR‑1260b inhibitor could significantly enhanced the chemoresponse of HCT116 cells to 5‑FU via reduced proliferation, increased apoptosis, and downregulation of PDCD4, p‑Akt and p‑ERK protein expression. In summary, the present study may provide a novel direction for future clinical therapy to enhance the chemosensitivity of tumor cells.

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