Long non-coding RNA LSAMP-1 is down-regulated in non-small cell lung cancer and predicts a poor prognosis.

Long non-coding RNA LSAMP-1 is down-regulated in non-small cell lung cancer and predicts a poor prognosis.
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长非编码RNA LSAMP-1在非小细胞肺癌中下调并预测不良预后

DOI:
10.1186/s12935-022-02592-0
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发表时间:
2022-05-06
影响因子:
5.8
通讯作者:
--
中科院分区:
医学2区
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长链非编码rna (lncRNAs)正在成为基因表达的主要调控因子,因此在人类肿瘤的发生和发展中起着至关重要的作用。但新型lncrna在非小细胞肺癌(NSCLC)中的作用在很大程度上仍未阐明。采用RT-qPCR方法检测Lnc-LSAMP-1在170例NSCLC及其邻近非肿瘤组织中的表达。通过体外和体内实验检测Lnc-LSAMP-1对细胞增殖、迁移、侵袭及药物敏感性的影响。通过RNA下拉实验确定了与lnc - lsamp -1相互作用的蛋白。利用rna测序技术鉴定Lnc-LSAMP-1在NSCLC中的潜在靶点。我们发现Lnc-LSAMP-1在170例NSCLC组织中与其邻近的非癌组织相比显著下调。Lnc-LSAMP-1表达缺失与NSCLC患者的不良预后显著相关。Lnc-LSAMP-1的异位表达显著抑制肺癌细胞的增殖、活力、侵袭和迁移能力,阻滞细胞周期,促进细胞凋亡。化疗增敏实验表明,过表达Lnc-LSAMP-1增强了TKI诱导的细胞增殖抑制作用。在机制上,Lnc-LSAMP-1-LSAMP形成一个复合物,可以保护LSAMP基因的降解,从而在NSCLC的进展和TKI靶向治疗中发挥重要作用。因此,我们的研究结果突出了Lnc-LSAMP-1在非小细胞肺癌中的功能和预后价值,并为非小细胞肺癌患者提供了潜在的新的治疗靶点和预后生物标志物。在线版本包含补充材料,可在10.1186/s12935-022-02592-0获得。
Long noncoding RNAs (lncRNAs) are emerging as master regulators for gene expression and thus play a vital role in human tumorigenesis and progression. But the involvement of novel lncRNAs in non-small cell lung cancer (NSCLC) remains largely unelucidated. A total of 170 NSCLC and their adjacent non-tumor tissues were enrolled to detect the expression of Lnc-LSAMP-1 by RT-qPCR. The effects of Lnc-LSAMP-1 on cell proliferation, migration, invasion and drug-sensitivity were determined by in vitro and in vivo experiments. The proteins that interact with Lnc-LSAMP-1were confirmed by RNA pull-down assay. RNA-sequencing were used to identify the potential targets of Lnc-LSAMP-1 in NSCLC. We found that Lnc-LSAMP-1 was significantly down-regulated in 170 cases of NSCLC tissues when compared to their adjacent non-cancerous tissues. Loss expression of Lnc-LSAMP-1 was notably correlated with unfavorable prognosis of NSCLC patients. The ectopic expression of Lnc-LSAMP-1 drastically inhibited lung cancer cell proliferation, viability, invasion and migration ability, arrested cell cycle and facilitated apoptosis. Chemotherapy sensitization experiments showed that over-expressed Lnc-LSAMP-1 enhanced the inhibition of cell proliferation induced by TKI. Mechanistically, Lnc-LSAMP-1-LSAMP formed a complex which could protect the degradation of LSAMP gene, and thus exerted crucial roles in NSCLC progression and TKI targeted treatment. Consequently, our findings highlight the function and prognostic value of Lnc-LSAMP-1 in NSCLC and provide potential novel therapeutic targets and prognostic biomarkers for patients with NSCLC. The online version contains supplementary material available at 10.1186/s12935-022-02592-0.
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