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Silencing of long noncoding RNA UCA1 inhibits colon cancer invasion, migration and epithelial-mesenchymal transition and tumour formation by upregulating miR-185-5p in vitro and in vivo.
Cell Biochemistry and Function ( IF 2.8 ) Pub Date : 2020-01-27 , DOI: 10.1002/cbf.3454
Chen Cao 1 , Junhui Zhang 1 , Chuanhua Yang 1 , Lili Xiang 1 , Wenneng Liu 2
Affiliation  

Colon cancer is the third most common malignancy in the world. Long-chain noncoding RNA urothelial carcinoma-associated 1 (UCA1) was abnormally expressed in colon cancer and participated in colon cancer by regulating multiple miRNAs. This study further explored the molecular mechanism of UCA1 in the development of colon cancer from both in vitro and in vivo. The results showed that UCA1 was highly expressed in colon cancer cells, while miR-185-5p was low expressed. Bioinformatics analysis showed that miR-185-5p was a target of UCA1, while MAPK14 was a target of miR-185-5p. Knockdown of UCA1 with shRNA (sh-UCA1) resulted in a significant increase in miR-185-5p and a significant decrease in MAPK14. In addition, sh-UCA1 inhibited invasion, migration and epithelial-mesenchymal transformation of colon cancer cells. Western blotting also showed that sh-UCA1 inactivated the MAPKAPK2/HSP27 pathway. Furthermore, animal studies have revealed that sh-UCA1 inhibited tumour formation in vivo and improved the survival rate of mice. Collectively, these results suggest that silencing UCA1 may inhibit the carcinogenesis and metastasis of colon cancer in vitro and in vivo by modulating miR-185-5p/MAPK14/MAPKAPK2/HSP27 axis. SIGNIFICANCE OF THE STUDY: Colon cancer is the third largest malignant tumour worldwide. This study elucidated the role of urothelial carcinoma-associated 1 (UCA1) in colon cancer cells and its molecular mechanism. The present study suggests that silencing UCA1 may inhibit the invasion, migration, epithelial-mesenchymal transformation and tumour formation of colon cancer by upregulating miR-185-5p in vitro and in vivo. In summary, this study provides a new strategy for targeted therapy of colon cancer.

中文翻译:

较长的非编码RNA UCA1的沉默通过在体内和体外上调miR-185-5p抑制结肠癌的侵袭,迁移以及上皮-间质转化和肿瘤形成。

结肠癌是世界上第三大最常见的恶性肿瘤。长链非编码RNA尿路上皮癌相关1(UCA1)在结肠癌中异常表达,并通过调节多种miRNA参与结肠癌。这项研究进一步探讨了UCA1在体内和体外发展结肠癌的分子机制。结果显示UCA1在结肠癌细胞中高表达,而miR-185-5p低表达。生物信息学分析表明,miR-185-5p是UCA1的靶标,而MAPK14是miR-185-5p的靶标。用shRNA(sh-UCA1)敲低UCA1导致miR-185-5p显着增加,MAPK14显着减少。此外,sh-UCA1抑制结肠癌细胞的侵袭,迁移和上皮-间质转化。Western印迹法还表明,sh-UCA1可以使MAPKAPK2 / HSP27途径失活。此外,动物研究表明,sh-UCA1在体内抑制肿瘤形成,并提高了小鼠的存活率。总体而言,这些结果表明沉默UCA1可能通过调节miR-185-5p / MAPK14 / MAPKAPK2 / HSP27轴在体外和体内抑制结肠癌的癌变和转移。研究的意义:结肠癌是全球第三大恶性肿瘤。这项研究阐明了尿路上皮癌相关1(UCA1)在结肠癌细胞中的作用及其分子机制。本研究表明沉默UCA1可能通过在体内外上调miR-185-5p来抑制结肠癌的侵袭,迁移,上皮-间质转化和肿瘤形成。综上所述,
更新日期:2020-01-27
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