MicroRNA‑936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway Retraction in /10.3892/or.2022.8389

Xu,Lishuai; Li,Weidong; Shi,Qian; Wang,Minfeng; Li,Heng; Yang,Xiaoli; Zhang,Junjun

doi:10.3892/or.2020.7456

MicroRNA‑936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway

Retraction in: /10.3892/or.2022.8389

Authors:
- Lishuai Xu
- Weidong Li
- Qian Shi
- Minfeng Wang
- Heng Li
- Xiaoli Yang
- Junjun Zhang
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Affiliations: Department of Ophthalmology and Optometry, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637100, P.R. China, Department of Ophthalmology, Yixing Eye Hospital, Yixing, Jiangsu 214200, P.R. China, Department of Ophthalmology, Suining Central Hospital, Suining, Sichuan 637000, P.R. China, Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: January 9, 2020 https://doi.org/10.3892/or.2020.7456
Pages: 635-645
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

MicroRNA‑936 (miR‑936) has been reported to play important roles in the progression of non‑small cell lung cancer and glioma. However, the expression and functions of miR‑936 in retinoblastoma (RB) remain elusive and need to be further elucidated. Herein, the aims were to measure miR‑936 expression in RB, identify the functional importance of miR‑936 in the oncogenicity of RB, and investigate the underlying molecular mechanisms. Reverse‑transcription quantitative PCR was carried out to determine miR‑936 expression in RB tissues and cell lines. Cell proliferation, colony formation, apoptosis, migration, and invasion in vitro and tumor growth in vivo were examined respectively by Cell Counting Kit‑8, colony formation, flow cytometric, and Transwell migration and invasion assays and a subcutaneous heterotopic xenograft experiment. The potential target of miR‑936 was predicted by bioinformatic analysis and was subsequently validated by luciferase reporter assay, reverse‑transcription quantitative PCR, and western blotting. miR‑936 expression was weak in both RB tissues and cell lines and was correlated with differentiation, lymph node metastasis and TNM staging in RB. RB cell proliferation, colony formation, migration, and invasion in vitro and tumor growth in vivo were attenuated by exogenous miR‑936, whereas apoptosis was enhanced by miR‑936 overexpression. Further molecular investigation identified histone deacetylase 9 (HDAC9) as a direct target gene of miR‑936 in RB cells. HDAC9 depletion had effects similar to those of miR‑936 overexpression in RB cells. Recovery of HDAC9 expression counteracted the tumor‑suppressive action of miR‑936 on the oncogenicity of RB cells. Ectopic miR‑936 expression deactivated the PI3K/AKT pathway in RB cells in vitro and in vivo by decreasing HDAC9 expression. Downregulated miR‑936 is related to poor prognosis in RB, and its upregulation inhibits RB aggressiveness via direct targeting of HDAC9 mRNA and thereby inactivation of the PI3K/AKT pathway.

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