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NEAT1 contributes to the CSC-like traits of A549/CDDP cells via activating Wnt signaling pathway
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-10-03 , DOI: 10.1016/j.cbi.2018.10.001
Pan Jiang , Hai Xu , Chuyue Xu , Aochang Chen , Lijun Chen , Ming Zhou , Ijaz ul Haq , Xiaoyue Wu , Zahula Mariyam , Qing Feng

Long non-coding RNAs (lncRNAs) have been identified to exert crucial roles in tumorigenesis and can serve as novel biomarkers for cancer therapy including lung cancer. Cisplatin is a first-line chemotherapeutic agent in non-small cell lung cancer (NSCLC), but the therapeutic effect is unsatisfactory, partly due to drug resistance. Emerging evidence showed that chemo-resistance is associated with acquisition of cancer stem cell (CSC)-like properties. Cisplatin resistance remains a major obstacle in the treatment of lung cancer, and its mechanism is still not fully elucidated. Meanwhile, CSCs have been involved in tumor metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) in modulating CSCs in lung cancer remains barely known. Therefore, we aimed to explore the correlation between NEAT1 and cancer stem cells in lung cancer. In our current study, we observed that CSC-like traits were much more enriched in cisplatin-resistant A549/CDDP cells. In addition, NEAT1 was obviously up-regulated in A549/CDDP cells compared with parental A549 cells. Knockdown of NEAT1 decreased the CSC-like properties of A549/CDDP cells through inhibiting tumor cell sphere volume, repressing CSC-like biomarkers levels and restraining CD44 positive cell ratios. Oppositely, overexpression of NEAT1 enhanced the stemness respectively. Moreover, it has been reported that Wnt pathway is implicated in many vital cellular functions including cancer stem cells. Here, it was exhibited that Wnt signal pathway was inactivated by knockdown of NEAT1 whereas activated by NEAT1 overexpression in A549/CDDP cells. Taken these together, it was indicated that NEAT1 could exert a novel biological role in NSCLC chemo-resistance.



中文翻译:

NEAT1通过激活Wnt信号通路促进A549 / CDDP细胞的CSC样性状

长期的非编码RNA(lncRNA)已被确定在肿瘤发生中起关键作用,并可作为包括肺癌在内的癌症治疗的新型生物标记。顺铂是非小细胞肺癌(NSCLC)的一线化疗药物,但治疗效果不理想,部分原因是耐药性。新兴证据表明,化学抗性与癌症干细胞(CSC)样特性的获得有关。顺铂耐药性仍然是治疗肺癌的主要障碍,其机理仍未完全阐明。同时,CSCs已经参与了肿瘤转移,肿瘤复发和化疗耐药性。到目前为止,尚不清楚核富集丰富的转录本1(NEAT1)调控肺癌CSCs的机制。所以,我们旨在探讨NEAT1与肺癌干细胞之间的相关性。在我们目前的研究中,我们观察到CSC样性状在顺铂耐药A549 / CDDP细胞中更加丰富。另外,与亲代A549细胞相比,NEAT1在A549 / CDDP细胞中明显上调。敲除NEAT1可通过抑制肿瘤细胞球体积,抑制CSC样生物标志物水平和抑制CD44阳性细胞比例来降低A549 / CDDP细胞的CSC样特性。相反,NEAT1的过表达分别增强了茎干。此外,据报道,Wnt途径涉及许多重要的细胞功能,包括癌症干细胞。在此,在A549 / CDDP细胞中,Wnt信号通路被NEAT1的敲低所灭活,而被NEAT1的过表达所激活。

更新日期:2018-10-03
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