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长链非编码RNA LSAMP-1在非小细胞肺癌中表达下调,并预示预后不良。

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

作者信息

Gong Wei, Li Yinyan, Xian Jianfeng, Yang Lei, Wang Yuanyuan, Zhang Xin, Zhou Yifeng, Wang Xinhua, Qiao Guibin, Chen Cuiyi, Datta Soham, Gao Xincheng, Lu Jiachun, Qiu Fuman

机构信息

The State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, China.

The School of Public Health, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.

出版信息

Cancer Cell Int. 2022 May 6;22(1):181. doi: 10.1186/s12935-022-02592-0.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

长链非编码RNA(lncRNAs)正逐渐成为基因表达的主要调节因子,因此在人类肿瘤发生和进展中起着至关重要的作用。但新型lncRNAs在非小细胞肺癌(NSCLC)中的作用仍 largely未阐明。

方法

共纳入170例NSCLC及其癌旁非肿瘤组织,通过RT-qPCR检测Lnc-LSAMP-1的表达。通过体外和体内实验确定Lnc-LSAMP-1对细胞增殖、迁移、侵袭和药物敏感性的影响。通过RNA下拉试验确认与Lnc-LSAMP-1相互作用的蛋白质。采用RNA测序鉴定NSCLC中Lnc-LSAMP-1的潜在靶点。

结果

我们发现,与癌旁非癌组织相比,170例NSCLC组织中Lnc-LSAMP-1显著下调。Lnc-LSAMP-1的缺失表达与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增殖、活力、侵袭和迁移能力,使细胞周期停滞并促进凋亡。化疗增敏实验表明,过表达的Lnc-LSAMP-1增强了TKI诱导的细胞增殖抑制作用。机制上,Lnc-LSAMP-1-LSAMP形成复合物,可保护LSAMP基因的降解,从而在NSCLC进展和TKI靶向治疗中发挥关键作用。

结论

因此,我们的研究结果突出了Lnc-LSAMP-1在NSCLC中的功能和预后价值,并为NSCLC患者提供了潜在的新型治疗靶点和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4feb/9074231/6952a7c5034b/12935_2022_2592_Fig1_HTML.jpg

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