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长链非编码 RNA 00960 通过 miR-124a/SphK1 轴促进肺腺癌的侵袭。

Long non-coding RNA 00960 promoted the aggressiveness of lung adenocarcinoma via the miR-124a/SphK1 axis.

机构信息

Weifang Medical University, Weifang, People's Republic of China.

Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, P.R. China.

出版信息

Bioengineered. 2022 Jan;13(1):1276-1287. doi: 10.1080/21655979.2021.1996507.

DOI:10.1080/21655979.2021.1996507
PMID:34738865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8805815/
Abstract

Long non-coding RNAs (lncRNAs) are closely associated with the development of lung adenocarcinoma (LADC). The present study focused on the role of LINC00960 in LADC. miRNA and mRNA expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cellular functions were evaluated by MTT, colony formation, and Transwell assays, respectively. LINC00960 Luciferase and RNA pull-down assays were performed to clarify the interaction between miR-124a and LINC00960 or Recombinant Sphingosine Kinase 1 (SphK1). We observed that LINC00960 was overexpressed in LADC tumor tissues and cell lines. LINC00960 knockdown suppressed the proliferation, migration, and invasion of LADC cells. Moreover, LINC00960 sponged miR-124a to inhibit the SphK1/S1P pathway in LADC cells. LINC00960 knockdown markedly reduced the rate of tumor growth. The luciferase reporter assay results demonstrated an interaction between miR-124a and LINC00960 or SphK1. This interaction was confirmed using the RNA pull-down assay. In addition, miR-124a downregulation or SphK1 upregulation reversed the inhibitory effects of LINC00960 knockdown on cellular functions of LADC cells, suggesting that LINC00960 may be a potential therapeutic biomarker for LADC via the miR-124a/SphK1 axis. Accordingly, LINC00960 may be a potential therapeutic biomarker for LADC.

摘要

长链非编码 RNA(lncRNA)与肺腺癌(LADC)的发生发展密切相关。本研究主要探讨 LINC00960 在 LADC 中的作用。采用实时荧光定量聚合酶链反应(qRT-PCR)检测 miRNA 和 mRNA 的表达水平。分别通过 MTT、集落形成和 Transwell 实验评估细胞功能。通过 LINC00960 荧光素酶和 RNA 下拉实验阐明 miR-124a 与 LINC00960 或重组鞘氨醇激酶 1(SphK1)之间的相互作用。我们观察到 LINC00960 在 LADC 肿瘤组织和细胞系中高表达。LINC00960 敲低抑制 LADC 细胞的增殖、迁移和侵袭。此外,LINC00960 海绵吸附 miR-124a 抑制 LADC 细胞中的 SphK1/S1P 通路。LINC00960 敲低显著降低肿瘤生长速度。荧光素酶报告基因实验结果表明 miR-124a 与 LINC00960 或 SphK1 之间存在相互作用。该相互作用通过 RNA 下拉实验得到证实。此外,miR-124a 下调或 SphK1 上调逆转了 LINC00960 敲低对 LADC 细胞功能的抑制作用,表明 LINC00960 可能通过 miR-124a/SphK1 轴成为 LADC 的潜在治疗性生物标志物。因此,LINC00960 可能是 LADC 的潜在治疗性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/d6b4aed93204/KBIE_A_1996507_F0007_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/f931f118dfe6/KBIE_A_1996507_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/d6b4aed93204/KBIE_A_1996507_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/0f1d847ebeef/KBIE_A_1996507_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/73ef79012d67/KBIE_A_1996507_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/5fea6e0047fe/KBIE_A_1996507_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/1518dc872577/KBIE_A_1996507_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/5ea39a2f72dd/KBIE_A_1996507_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8810/8805815/f931f118dfe6/KBIE_A_1996507_F0006_OC.jpg
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