lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

Guo,Haiyan; Lin,Shufang; Gan,Zhenyong; Xie,Jinglian; Zhou,Jiaming; Hu,Ming

doi:10.3892/ol.2021.13114

lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

Authors:
- Haiyan Guo
- Shufang Lin
- Zhenyong Gan
- Jinglian Xie
- Jiaming Zhou
- Ming Hu
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Affiliations: Department of Respiratory Medicine, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China, Department of Respiratory Medicine, The Fifth People's Hospital of Nanhai District, Foshan, Guangdong 528200, P.R. China, Department of Urology, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China
Published online on: October 26, 2021 https://doi.org/10.3892/ol.2021.13114
Article Number: 853
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3‑AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3‑AS1 in cancer development has not yet been fully elucidated. The present study focused on non‑small cell lung cancer (NSCLC) in order to gain insight into how FOXD3‑AS1 drives cancer progression. First, FOXD3‑AS1 expression in NSCLC tissue samples was detected using reverse transcription‑quantitative (RT‑qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit‑8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3‑AS1 and microRNA (miR)‑135a‑5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3‑AS1 in tumor growth. FOXD3‑AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3‑AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh‑NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3‑AS1 and miR‑135a‑5p. Moreover, FOXD3‑AS1 silencing led to the upregulation of miR‑135a‑5p in A549 and H1229 cells compared with sh‑NC group. It was also demonstrated that miR‑135a‑5p could bind to the 3' untranslated region of cyclin‑dependent kinase 6 (CDK6) and negatively modulate its transcription. miR‑135a‑5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3‑AS1 knockdown. Altogether, the present study suggests that FOXD3‑AS1 sponges miR‑135a‑5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.

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