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长链非编码RNA OR3A4通过上调CDK1促进非小细胞肺癌的顺铂耐药性。

Long noncoding RNA OR3A4 promotes cisplatin resistance of non-small cell lung cancer by upregulating CDK1.

作者信息

Shang J, Xu Y-D, Zhang Y-Y, Li M

机构信息

Department of Central Sterile Supply, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 May;23(10):4220-4225. doi: 10.26355/eurrev_201905_17926.

DOI:10.26355/eurrev_201905_17926
PMID:31173293
Abstract

OBJECTIVE

Numerous studies have proved that long non-coding RNAs (lncRNAs) have an important role in malignant tumors, including non-small cell lung cancer (NSCLC). LncRNA olfactory receptor family 3 subfamily A member 4 (OR3A4) was explored to identify how it functions in resistance of NSCLC patients to cisplatin.

MATERIALS AND METHODS

Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect OR3A4 expression in NSCLC patients. Then, we conducted Cell Counting Kit-8 (CCK-8) assay and flow cytometric analysis to detect the function of OR3A4 on the resistance of NSCLC cells to cisplatin. Furthermore, the potential mechanism was explored by mechanism assays.

RESULTS

Compared with OR3A4 expression of paired A549 cells, OR3A4 expression of A549/DDP cells was higher. Moreover, the functional assay showed that after OR3A4 was silenced in A549/DDP cells, cell cycle arrest and cell apoptosis was induced, and resistance to cisplatin was reversed. Furthermore, it was found that CDK1 expression was suppressed in A549/DDP cells by knockdown of OR3A4.

CONCLUSIONS

The present work suggests that OR3A4 participates in regulating cell cycle, cell apoptosis of NSCLC cells and the resistance to cisplatin via upregulating CDK1, indicating that OR3A4 could be identified as a potential therapeutic target for NSCLC patients.

摘要

目的

众多研究已证明长链非编码RNA(lncRNA)在恶性肿瘤中发挥重要作用,包括非小细胞肺癌(NSCLC)。本研究旨在探究lncRNA嗅觉受体家族3亚家族A成员4(OR3A4)在NSCLC患者对顺铂耐药中的作用机制。

材料与方法

采用实时定量聚合酶链反应(RT-qPCR)检测NSCLC患者中OR3A4的表达。然后,通过细胞计数试剂盒-8(CCK-8)检测和流式细胞术分析,检测OR3A4对NSCLC细胞顺铂耐药性的影响。此外,通过机制分析探究其潜在机制。

结果

与配对的A549细胞中OR3A4表达相比,A549/DDP细胞中OR3A4表达更高。此外,功能分析表明,在A549/DDP细胞中沉默OR3A4后,可诱导细胞周期阻滞和细胞凋亡,并逆转对顺铂的耐药性。此外,发现敲低OR3A4可抑制A549/DDP细胞中CDK1的表达。

结论

本研究表明,OR3A4通过上调CDK1参与调节NSCLC细胞的细胞周期、细胞凋亡及对顺铂的耐药性,提示OR3A4可作为NSCLC患者潜在的治疗靶点。

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