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长链非编码RNA AGAP2-AS1通过与LINC-PINT形成负反馈环促进结肠癌细胞增殖、迁移和侵袭。

LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT.

作者信息

Ji Liechen, Chen Shuo, Gu Liqiang, Wang Juan, Zhang Xipeng

机构信息

Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, People's Republic of China.

Department of General Surgery, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Mar 2;13:2153-2161. doi: 10.2147/CMAR.S260371. eCollection 2021.

Abstract

INTRODUCTION

It has been reported that lncRNA AGAP2-AS1 promotes the development of gastric cancer, lung cancer and breast cancer. This study aimed to investigate the role of AGAP2-AS1 in colon cancer.

METHODS

A total of 66 patients with colon cancer were enrolled. RT-qPCR was performed to detect the differential expression of AGAP2-AS1 in tumor tissues and adjacent normal tissues. To test the interaction between AGAP2-AS1 and LINC-PINT in colon cancer, overexpression vector or inhibitor of AGAP2-AS1 and LINC-PINT were transfected into RKO and HCT 116 cells. CCK-8 assay was used to detect cell proliferation. Transwell assays were performed to evaluate cell migration and invasion. The expression of p-LATS1, p-YAP and nuclear YAP were detected by Western blot and immunofluorescence.

RESULTS

The expression of AGAP2-AS1 was upregulated in colon cancer tissues compared with that in adjacent normal tissues, and the expression of AGAP2-AS1 in colon cancer tissues was not significantly affected by tumor stages. In addition, we found that the expression of LINC-PINT was downregulated in colon cancer tissues compared with that in adjacent normal tissues and had a reverse correlation with the expression of AGAP2-AS1 in colon cancer tissues. Moreover, overexpression of AGAP2-AS1 downregulated the expression of LINC-PINT, and overexpression of LINC-PINT also altered the expression of AGAP2-AS1 in colon cancer cells. Inhibition of AGAP2-AS1 upregulated the expression of LINC-PINT, and inhibition of LINC-PINT promoted the expression levels of AGAP2-AS1 in colon cancer cells. Furthermore, overexpression of AGAP2-AS1 could increase the proliferation, invasion and migration of colon cancer cells, while overexpression of LINC-PINT could attenuate the effects of overexpression of AGAP2-AS1 on the proliferation, migration and invasion of colon cancer cells. We also found that AGAP2-AS1 promoted colon cancer cell proliferation, migration and invasion through the Hippo signaling.

CONCLUSION

Upregulated expression of AGAP2-AS1 promoted proliferation, invasion and migration in colon cancer by forming a negative feedback loop with LINC-PINT.

摘要

引言

据报道,长链非编码RNA(lncRNA)AGAP2-AS1促进胃癌、肺癌和乳腺癌的发展。本研究旨在探讨AGAP2-AS1在结肠癌中的作用。

方法

共纳入66例结肠癌患者。采用逆转录定量聚合酶链反应(RT-qPCR)检测AGAP2-AS1在肿瘤组织及癌旁正常组织中的差异表达。为检测结肠癌中AGAP2-AS1与LINC-PINT之间的相互作用,将AGAP2-AS1和LINC-PINT的过表达载体或抑制剂转染至RKO和HCT 116细胞中。采用细胞计数试剂盒-8(CCK-8)法检测细胞增殖。进行Transwell实验评估细胞迁移和侵袭能力。通过蛋白质免疫印迹法和免疫荧光法检测磷酸化LATS1(p-LATS1)、磷酸化YAP(p-YAP)和细胞核YAP的表达。

结果

与癌旁正常组织相比,AGAP2-AS1在结肠癌组织中的表达上调,且AGAP2-AS1在结肠癌组织中的表达不受肿瘤分期的显著影响。此外,我们发现与癌旁正常组织相比,LINC-PINT在结肠癌组织中的表达下调,且与结肠癌组织中AGAP2-AS1的表达呈负相关。此外,AGAP2-AS1的过表达下调了LINC-PINT的表达,LINC-PINT的过表达也改变了结肠癌细胞中AGAP2-AS1的表达。抑制AGAP2-AS1可上调LINC-PINT的表达,抑制LINC-PINT可促进结肠癌细胞中AGAP2-AS1的表达水平。此外,AGAP2-AS1的过表达可增加结肠癌细胞的增殖、侵袭和迁移能力,而LINC-PINT的过表达可减弱AGAP2-AS1过表达对结肠癌细胞增殖、迁移和侵袭的影响。我们还发现AGAP2-AS1通过Hippo信号通路促进结肠癌细胞的增殖、迁移和侵袭。

结论

AGAP2-AS1的表达上调通过与LINC-PINT形成负反馈环促进结肠癌的增殖、侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de58/7936697/54a19574935e/CMAR-13-2153-g0001.jpg

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