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长链非编码 RNA PTPRG 反义 RNA 1 通过调节 miR-200c-3p/TCF4 降低非小细胞肺癌细胞的放射敏感性。

Long Noncoding RNA PTPRG Antisense RNA 1 Reduces Radiosensitivity of Nonsmall Cell Lung Cancer Cells Via Regulating MiR-200c-3p/TCF4.

机构信息

Department of Oncology, People's Hospital, Xintai, China.

Department of Geratology, Shanxi Cancer Hospital, Taiyuan, China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820942615. doi: 10.1177/1533033820942615.

Abstract

BACKGROUND

PTPRG antisense RNA 1 has been well-documented to exert an oncogenic role in diverse neoplasms. However, the precise role of PTPRG antisense RNA 1 in regulating radiosensitivity of nonsmall cell lung cancer cells remains largely elusive.

METHODS

Expression levels of PTPRG antisense RNA 1 and miR-200c-3p in nonsmall cell lung cancer tissues and cells were detected by quantitative real-time polymerase chain reaction, while transcription factor 4 expression was examined by immunohistochemistry and Western blot. After nonsmall cell lung cancer cells were exposed to X-ray with different doses , Cell Counting Kit8 assay and colony formation assay were conducted to determine the influence of PTPRG antisense RNA 1 on cell viability. Interaction between miR-200c-3p and PTPRG antisense RNA 1 as well as transcription factor 4 was investigated by dual luciferase reporter assay.

RESULT

In nonsmall cell lung cancer tissues, the expressions of PTPRG antisense RNA 1 and transcription factor 4 were significantly upregulated, whereas the expression of miR-200c-3p was downregulated. It was also proved that PTPRG antisense RNA 1 and 3'-untranslated region of transcription factor 4 can bind to miR-200c-3p. Under X-ray irradiation, overexpressed PTPRG antisense RNA 1 could promote the viability and enhance the radioresistance of nonsmall cell lung cancer cells, and this effect was partially weakened by miR-200c-3p mimics. Transcription factor 4 was identified as a target gene of miR-200c-3p, which could be positively regulated by PTPRG antisense RNA 1.

CONCLUSION

PTPRG antisense RNA 1 reduces the radiosensitivity of nonsmall cell lung cancer cells via modulating miR-200c-3p/TCF4 axis.

摘要

背景

已有充分文献证明 PTPRG 反义 RNA1 在多种肿瘤中发挥致癌作用。然而,PTPRG 反义 RNA1 在调节非小细胞肺癌细胞放射敏感性中的确切作用在很大程度上仍不清楚。

方法

采用实时定量聚合酶链反应检测非小细胞肺癌组织和细胞中 PTPRG 反义 RNA1 和 miR-200c-3p 的表达水平,采用免疫组织化学和 Western blot 检测转录因子 4 的表达水平。在非小细胞肺癌细胞接受不同剂量 X 射线照射后,通过细胞计数试剂盒 8 检测和集落形成实验检测 PTPRG 反义 RNA1 对细胞活力的影响。通过双荧光素酶报告基因实验研究 miR-200c-3p 与 PTPRG 反义 RNA1 以及转录因子 4 之间的相互作用。

结果

在非小细胞肺癌组织中,PTPRG 反义 RNA1 和转录因子 4 的表达明显上调,而 miR-200c-3p 的表达下调。研究还证实,PTPRG 反义 RNA1 和转录因子 4 的 3'非翻译区可以与 miR-200c-3p 结合。在 X 射线照射下,过表达的 PTPRG 反义 RNA1 可促进非小细胞肺癌细胞的活力并增强其放射抗性,而 miR-200c-3p 模拟物可部分减弱这种作用。转录因子 4 被鉴定为 miR-200c-3p 的靶基因,其可被 PTPRG 反义 RNA1 正向调控。

结论

PTPRG 反义 RNA1 通过调节 miR-200c-3p/TCF4 轴降低非小细胞肺癌细胞的放射敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d618/7672737/a1c665219384/10.1177_1533033820942615-fig1.jpg

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