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Long Non-Coding RNA GAS5 Suppresses Tumor Progression and Enhances the Radiosensitivity of Prostate Cancer Through the miR-320a/RAB21 Axis

Authors Ma X, Wang Z, Ren H, Bao X, Zhang Y, Wang B, Ruan D

Received 30 December 2019

Accepted for publication 30 July 2020

Published 22 September 2020 Volume 2020:12 Pages 8833—8845


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo

Xiulong Ma,1 Zhongwei Wang,1 Hongtao Ren,1 Xing Bao,1 Yang Zhang,1 Baofeng Wang,1 Dongli Ruan2

1Department of Radiation Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Urology, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China

Correspondence: Dongli Ruan Tel +86-29-84775507

Background: Long non-coding RNAs (lncRNAs) function as a class of significant mediators in prostate cancer (PCa), and this study mainly discussed the molecular mechanism of lncRNA growth arrest-specific 5 (GAS5) in PCa progression and radiosensitivity.
Materials and Methods: GAS5 and microRNA-320a (miR-320a) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and migration were severally examined through 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and transwell assays. PCa cells were treated with X-ray irradiation. Cell survival and apoptosis rate were assayed using colony formation assay and flow cytometry, respectively. The apoptosis-related protein and Rab GTPase 21 (RAB21) protein levels were measured by Western blot. The relation between miR-320a and GAS5 or RAB21 was assessed via the dual-luciferase reporter assay. The effect of GAS5 on radiosensitivity of PCa in vivo was evaluated by xenotransplantation assay.
Results: GAS5 was down-regulated in PCa tissues and cells. GAS5 overexpression suppressed cell viability and migration while facilitated radiosensitivity of PCa cells. GAS5 was a molecular sponge of miR-320a. The effects of GAS5 up-regulation on PCa cells were accomplished by sponging miR-320a. MiR-320a targeted RAB21 and GAS5 up-regulated RAB21 expression via targeting miR-320a. RAB21 knockdown reversed the effects of miR-320a inhibition on PCa cells. GAS5 promoted the radiosensitivity of PCa by the miR-320a/RAB21 axis in vivo.
Conclusion: Collectively, GAS5 restrained tumor development and expedited the radiosensitivity in PCa by the miR-320a/RAB21 axis, which provided a molecular regulatory mechanism of GAS5/miR-320a/RAB21 in PCa development and radioresistance.

Keywords: GAS5, prostate cancer, radiosensitivity, miR-320a, RAB21

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