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LOXL1-AS1通过调控miR-3128/RHOXF2轴促进非小细胞肺癌进展。

LOXL1-AS1 Contributes to Non-Small Cell Lung Cancer Progression by Regulating miR-3128/RHOXF2 Axis.

作者信息

Zhao Limin, Zhang Xuefei, Guo Huannan, Liu Mingyang, Wang Liming

机构信息

Department of Oncology, General Hospital of Heilongjiang General Administration of Agriculture and Reclamation, Harbin 150088, People's Republic of China.

Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 25;13:6063-6071. doi: 10.2147/OTT.S247900. eCollection 2020.

Abstract

PURPOSE

The purpose of this study was to investigate the molecular mechanism of LncRNA LOXL1-AS1 in non-small cell lung cancer (NSCLC).

METHODS

Lung cancer cell lines (H1299, A549, H520 and H596) and human normal lung epithelial cell line (BEAS-2B) were used in this study. Gene expression was measured by qRT-PCR (quantitative real-time PCR). The bioinformatics databases (miRDB and TargetScan7) were used to predict target genes. Luciferase assay and pull-down assay were processed for verifying the binding sites. CCK8 assay was used for detecting proliferation, and transwell assay was undertaken for migration and invasion.

RESULTS

LncRNA LOXL1-AS1 was higher expressed in lung cancer tissues and cells. Moreover, LOXL1-AS1 expression was upregulated in tumor tissues with advanced stages and metastasis. After knocking down LOXL1-AS1, proliferation, invasion and migration of H1299 and A549 cells were inhibited. Interestingly, miR-3128 was negatively regulated by LncRNA LOXL1-AS1, which inhibited the expression of RHOXF2. Rescue assay also confirmed that miR-3128 inhibitor and oeRHOXF2 could rescue the effect of down-regulated LOXL1-AS1 on proliferation, invasion and migration progression.

CONCLUSION

LOXL1-AS1 promotes the progression of NSCLC by regulating miR-3128/RHOXF2 axis, which might be a new potential target for the diagnosis and treatment of NSCLC.

摘要

目的

本研究旨在探讨长链非编码RNA LOXL1-AS1在非小细胞肺癌(NSCLC)中的分子机制。

方法

本研究使用了肺癌细胞系(H1299、A549、H520和H596)以及人正常肺上皮细胞系(BEAS-2B)。通过qRT-PCR(定量实时聚合酶链反应)检测基因表达。利用生物信息学数据库(miRDB和TargetScan7)预测靶基因。进行荧光素酶报告基因检测和下拉实验以验证结合位点。采用CCK8实验检测细胞增殖,采用Transwell实验检测细胞迁移和侵袭能力。

结果

LncRNA LOXL1-AS1在肺癌组织和细胞中高表达。此外,LOXL1-AS1在晚期和有转移的肿瘤组织中表达上调。敲低LOXL1-AS1后,H1299和A549细胞的增殖、侵袭和迁移能力受到抑制。有趣的是,miR-3128受LncRNA LOXL1-AS影响呈负调控,进而抑制RHOXF2的表达。挽救实验也证实,miR-3128抑制剂和过表达RHOXF2可挽救下调LOXL1-AS1对增殖、侵袭和迁移进程的影响。

结论

LOXL1-AS1通过调控miR-3128/RHOXF2轴促进NSCLC进展,这可能是NSCLC诊断和治疗的一个新的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40d0/7326695/c6f8bbc11bd1/OTT-13-6063-g0002.jpg

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