Xu Ran, Liu Tianhua, Zuo Ling, Guo Dongqing, Ye Guancheng, Jiang Jingjing, Yu Xue, Zhang Shujing, Hou Chunying
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Biochem Biophys Rep. 2021 Aug 30;28:101122. doi: 10.1016/j.bbrep.2021.101122. eCollection 2021 Dec.
Therapies for lung adenocarcinoma (LUAD) are mainly limited by drug resistance, metastasis or recurrence related to cancer stem cells (CSCs) with high proliferation and self-renewing. This research validated that miR-31 was over-expressed in LUAD by the analysis of generous clinical samples data. And the results of clinical data analysis showed that high expression of miR-31 was more common in patients with worse prognosis. The genes differentially expressed in LUAD tissues compared with normal tissues and A549CD133 cells (LUAD CSCs) compared with A549 cells were separately screened from Gene Expression Profiling Interactive Analysis and GEO datasets. The target genes that may play a role in the regulation of lung adenocarcinoma was screened by comparison between the differential genes and the target genes of miR-31. The functional enrichment analysis of GO Biological Processes showed that the expression of target genes related to cell proliferation was increased, while the expression of target genes related to cell invasion and metastasis was decreased in LUAD tissues and A549CD133 cells. The results suggested that miR-31 may have a significant inhibitory effect on the differentiation, invasion, metastasis and adhesion of LUAD CSCs, which was verified and experiments. Knock down of miR-31 accelerated xenograft tumor growth and liver metastasis . Likewise, the carcinogenicity, invasion and metastasis of A549CD133 CSCs were promoted after miR-31 knockdown. The study validated that miR-31 was up regulated in LUAD and its expression may affect the survival time of patients with lung adenocarcinoma, which indicated that miR-31 may have potential value for diagnosis and prognosis of LUAD. However, the inhibitory effect of miR-31 on tumorigenesis, invasion and metastasis of lung adenocarcinoma CSCs suggested its complexity in the regulation of lung adenocarcinoma, which may be related to its extensive regulation of various target genes.
肺腺癌(LUAD)的治疗主要受限于与具有高增殖和自我更新能力的癌症干细胞(CSCs)相关的耐药性、转移或复发。本研究通过分析大量临床样本数据验证了miR-31在LUAD中过表达。临床数据分析结果显示,miR-31高表达在预后较差的患者中更为常见。分别从基因表达谱交互式分析和GEO数据集中筛选出LUAD组织与正常组织相比以及A549CD133细胞(LUAD CSCs)与A549细胞相比差异表达的基因。通过差异基因与miR-31靶基因的比较筛选出可能在肺腺癌调控中起作用的靶基因。GO生物过程的功能富集分析表明,LUAD组织和A549CD133细胞中与细胞增殖相关的靶基因表达增加,而与细胞侵袭和转移相关的靶基因表达降低。结果表明,miR-31可能对LUAD CSCs的分化、侵袭、转移和黏附具有显著抑制作用,这在实验中得到了验证。敲低miR-31加速了异种移植肿瘤的生长和肝转移。同样,miR-31敲低后促进了A549CD133 CSCs的致癌性、侵袭和转移。该研究验证了miR-31在LUAD中上调,其表达可能影响肺腺癌患者的生存时间,这表明miR-31可能对LUAD的诊断和预后具有潜在价值。然而,miR-31对肺腺癌CSCs肿瘤发生、侵袭和转移的抑制作用表明其在肺腺癌调控中的复杂性,这可能与其对各种靶基因的广泛调控有关。