Long non‑coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR‑9‑3p in hepatocellular carcinoma

Guan,Qiang; Yuan,Bo; Zhang,Xiaobin; Yan,Tinghai; Li,Jiangong; Xu,Wuzhong

doi:10.3892/etm.2021.10187

Long non‑coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR‑9‑3p in hepatocellular carcinoma

Authors:
- Qiang Guan
- Bo Yuan
- Xiaobin Zhang
- Tinghai Yan
- Jiangong Li
- Wuzhong Xu
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Affiliations: Department of Hepatobiliary Surgery, People's Hospital of Dongying, Dongying, Shandong 257091, P.R. China, Department of Oncology, People's Hospital of Wudi, Binzhou, Shandong 251900, P.R. China
Published online on: May 12, 2021 https://doi.org/10.3892/etm.2021.10187
Article Number: 755
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‑related death worldwide with a low 5‑year survival rate. Long non‑coding RNA (lncRNA) double homeobox A pseudogene 8 (DUXAP8) is an oncogene and a potential biomarker in various tumors, such as ovarian, colorectal and non‑small‑cell lung cancer. However, the function and molecular mechanism underlying DUXAP8 in HCC progression is not completely understood. The expression of DUXAP8, microRNA (miR)‑9‑3p and insulin‑like growth factor 1 receptor (IGF1R) in HCC tissues and cells was detected via reverse transcription‑quantitative PCR. The expression levels of IGF1R and epithelial‑mesenchymal transition‑associated proteins (Snail, Slug, E‑cadherin, N‑cadherin and vimentin) were assessed via western blotting. The effects of DUXAP8, miR‑9‑3p and IGF1R on proliferation, migration and invasion were examined by conducting Cell Counting Kit‑8 and Transwell assays, respectively. The interaction between miR‑9‑3p and DUXAP8 or IGF1R was predicted using StarBase or TargetScan, and further assessed using dual luciferase reporter and RNA immunoprecipitation assays. DUXAP8 and IGF1R were upregulated and miR‑9‑3p was downregulated in HCC tissues and cells compared with adjacent healthy tissues and a normal liver cell line, respectively. miR‑9‑3p overexpression decreased the protein expression level of IGF1R, and miR‑9‑3p knockdown enhanced the protein expression level of IGF1R in HCC cells compared with the corresponding control groups. Moreover, compared with the corresponding control groups, DUXAP8 knockdown and miR‑9‑3p overexpression increased E‑cadherin protein expression levels, and decreased Snail, Slug, N‑cadherin and vimentin protein expression levels. However, miR‑9‑3p inhibitor and IGF1R overexpression reversed DUXAP8 knockdown‑ and miR‑9‑3p overexpression‑induced effects, respectively. In addition, compared with the corresponding control groups, DUXAP8 knockdown and miR‑9‑3p overexpression suppressed proliferation, migration and invasion, which was reversed by miR‑9‑3p inhibitor and IGF1R overexpression, respectively. Moreover, miR‑9‑3p as the target of DUXAP8 and IGF1R as the target of miR‑9‑3p were verified in HCC cells. lncRNA DUXAP8 contributed to HCC tumorigenesis via the miR‑9‑3p/IGF1R axis, providing a novel therapeutic approach for HCC diagnosis and treatment.

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