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环状RNA PLEC作为微小RNA-198的海绵,促进胃癌细胞对紫杉醇的抗性和肿瘤发生。

Circular RNA PLEC acts as a sponge of microRNA-198 to promote gastric carcinoma cell resistance to paclitaxel and tumorigenesis.

作者信息

Zhou Ning, Wang Wei, Xu Chunlei, Yu Wenyan

机构信息

Digestive System Department of Affiliated Tumor Hospital of Xinjiang Medical University, PR China.

Department Pathophysiology, College of Preclinical Medicine, Xinjiang Medical University, PR China.

出版信息

Pathol Res Pract. 2021 Aug;224:153487. doi: 10.1016/j.prp.2021.153487. Epub 2021 May 18.

Abstract

Gastric carcinoma (GC) is one of the most frequent types of malignancy worldwide. Resistance to paclitaxel (PTX) has become an obstacle to the prognosis of GC, and the underlying mechanism is not clear. A previous study identified GC-related circRNAs via microarray analysis and bioinformatics analysis, and we discovered that circPLEC (hsa_circ_104722) was markedly upregulated in GC tissues and cells. The molecular mechanism of circPLEC in PTX-resistant GC cells still needs to be explored. In the present study, qRT-PCR demonstrated that circPLEC was upregulated in PTX-resistant GC tissues and cells, indicating that circPLEC boosts the PTX resistance of GC. circPLEC downregulation weakened GC resistance to PTX and tumorigenesis, migration and invasion and promoted the apoptosis of PTX-resistant GC cells. MiR-198 inhibitor reversed the effect of circPLEC downreguAlation in PTX-resistant GC cells, and MUC19 downregulation weakened GC resistance to PTX and tumorigenesis and improved the apoptosis of PTX-resistant GC cells. In summary, circPLEC acts as a sponge of miR-198 to promote the PTX resistance and tumorigenesis of GC cells by regulating MUC19 expression.

摘要

胃癌(GC)是全球最常见的恶性肿瘤类型之一。对紫杉醇(PTX)耐药已成为影响GC预后的障碍,其潜在机制尚不清楚。先前的一项研究通过微阵列分析和生物信息学分析鉴定了与GC相关的环状RNA,我们发现环状PLEC(hsa_circ_104722)在GC组织和细胞中显著上调。环状PLEC在耐PTX的GC细胞中的分子机制仍有待探索。在本研究中,qRT-PCR表明环状PLEC在耐PTX的GC组织和细胞中上调,表明环状PLEC增强了GC对PTX的耐药性。环状PLEC下调减弱了GC对PTX的耐药性以及肿瘤发生、迁移和侵袭,并促进了耐PTX的GC细胞凋亡。miR-198抑制剂逆转了环状PLEC下调对耐PTX的GC细胞的影响,而MUC19下调减弱了GC对PTX的耐药性和肿瘤发生,并改善了耐PTX的GC细胞凋亡。总之,环状PLEC作为miR-198的海绵,通过调节MUC19表达促进GC细胞的PTX耐药性和肿瘤发生。

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