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长链非编码 RNA GAS5 通过 miR-217/LHPP 轴降低非小细胞肺癌的顺铂耐药性。

The long intergenic noncoding RNA GAS5 reduces cisplatin-resistance in non-small cell lung cancer through the miR-217/LHPP axis.

机构信息

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Department of Thoracic Surgery, Ningbo First Hospital, Ningbo, China.

出版信息

Aging (Albany NY). 2021 Jan 8;13(2):2864-2884. doi: 10.18632/aging.202352.

DOI:10.18632/aging.202352
PMID:33418541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7880381/
Abstract

Long noncoding RNAs (lncRNAs) are known to exert their effects to tumor progression. In this study, the role of the lncRNA GAS5 (growth arrest specific 5) was confirmed in reducing non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance. In NSCLC tissue samples, GAS5 expression decreased significantly. Low GAS5 levels were positively correlated with NSCLC characteristics including TNM, tumor size and lymphatic metastasis. Functionally, GAS5 significantly reduced NSCLC/DDP cell migration, invasion and epithelial-mesenchymal transition (EMT) progression . , GAS5 upregulation inhibited remarkably NSCLC/DDP cell tumor growth. Mechanism analysis suggested that GAS5 was a molecular sponge of miR-217, inhibiting the expression of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). In conclusion, this study reveals that the GAS5/miR-217/LHPP pathway reduces NSCLC cisplatin resistance and that LHPP may serve as a potential therapeutic target for NSCLC cisplatin resistance.

摘要

长链非编码 RNA（lncRNA）已知可发挥作用促进肿瘤进展。在这项研究中，证实了 lncRNA GAS5（生长停滞特异性 5）在降低非小细胞肺癌（NSCLC）顺铂（DDP）耐药性中的作用。在 NSCLC 组织样本中，GAS5 的表达显著降低。低水平的 GAS5 与 NSCLC 的特征呈正相关，包括 TNM、肿瘤大小和淋巴转移。功能上，GAS5 显著降低 NSCLC/DDP 细胞的迁移、侵袭和上皮-间充质转化（EMT）进展。上调 GAS5 显著抑制 NSCLC/DDP 细胞的肿瘤生长。机制分析表明，GAS5 是 miR-217 的分子海绵，抑制磷酸丝氨酸磷酸组氨酸无机焦磷酸磷酸酶（LHPP）的表达。总之，本研究揭示了 GAS5/miR-217/LHPP 通路降低 NSCLC 顺铂耐药性，LHPP 可能成为 NSCLC 顺铂耐药性的潜在治疗靶点。

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