miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

Guo,Fangdong; Zhu,Xiaoyu; Zhao,Qingquan; Huang,Qirong

doi:10.3892/ijmm.2020.4666

miR‑589‑3p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R

Authors:
- Fangdong Guo
- Xiaoyu Zhu
- Qingquan Zhao
- Qirong Huang
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Affiliations: Department of Breast and Thyroid Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Breast and Thyroid Surgery, The 2nd Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China, Department of Breast and Thyroid Surgery, Chengdu Dongli Hospital, Chengdu, Sichuan 610000, P.R. China
Published online on: July 2, 2020 https://doi.org/10.3892/ijmm.2020.4666
Pages: 989-1002
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The long non‑coding (lnc)RNA named tissue differentiation inducing non‑protein coding RNA (TINCR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINCR‑targeting micro (mi)RNAs and the regulatory mechanisms of TINCR in breast cancer. Following prediction by TargetScan and confirmation by dual‑luciferase reporter assay, TINCR was demonstrated to be a target gene for miR‑589‑3p. The expression of TINCR and miR‑589‑3p in breast cancer and adjacent tissues was detected by reverse transcription‑quantitative (RT‑q)PCR, and the correlation between TINCR and miR‑589‑3p expression was determined by using Spearman correlation analysis. The 5‑years survival was analyzed in patients with breast cancer according to TINCR expression (high or low). The effects of TINCR and miR‑589‑3p on the proliferation, apoptosis, migratory and invasive abilities of some breast cancer cell lines were detected by MTT assay, flow cytometry, wound healing assay and Transwell assay. The target gene of miR‑589‑3p was predicted and verified by TargetScan and dual‑luciferase reporter assay, and the mechanism of miR‑589‑3p involvement in breast cancer cells was explored by overexpression or downregulation of miR‑589‑3p in breast cancer cells. RT‑qPCR and western blotting were used to determine the expression of the insulin‑like growth factor 1 receptor (IGF1R)/AKT pathway‑related genes. The results demonstrated that TINCR expression level was negatively correlated with miR‑589‑3p expression level in breast cancer tissues and that patients with high expression of TINCR presented with lower survival rates. In addition, TINCR overexpression in cancer cells inhibited miR‑589‑3p expression, and cell transfection with miR‑589‑3p mimic partially reversed the effect of TINCR overexpression on the promotion of cancer cell proliferation, migration and invasion, and on the inhibition of cancer cell apoptosis. Furthermore, IGF1R, which is a target gene of miR‑589‑3p, increased cancer cell proliferation, migration and invasion and inhibited cancer cell apoptosis; however, these effects were partially reversed by miR‑589‑3p mimic. Furthermore, the results demonstrated that miR‑589‑3p mimic could downregulate the protein expression of IGF1R and p‑AKT. In addition, TINCR overexpression downregulated miR‑589‑3p expression level. miR‑589‑3p partially reversed the effects of TINCR overexpression on cancer cell proliferation, migration and invasion, and inhibited cancer cell apoptosis by inhibiting the IGF1R‑Akt pathway. The results from the present study demonstrated that TINCR may sponge miR‑589‑3p in order to inhibit IGF1R‑Akt pathway activation in breast cancer cells, promoting therefore cancer cell proliferation, migration and invasion.

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