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长链非编码RNA-BLACAT1通过EZH2诱导的H3K27me3抑制CDKN1C促进胰腺癌细胞的增殖、迁移及有氧糖酵解。

LncRNA-BLACAT1 Facilitates Proliferation, Migration and Aerobic Glycolysis of Pancreatic Cancer Cells by Repressing CDKN1C via EZH2-Induced H3K27me3.

作者信息

Zhou Xin, Gao Wei, Hua Huanhuan, Ji Zhimin

机构信息

Department of Oncology, Linyi People's Hospital, Linyi, China.

Department of Clinical Laboratory, Linyi People's Hospital, Linyi, China.

出版信息

Front Oncol. 2020 Sep 23;10:539805. doi: 10.3389/fonc.2020.539805. eCollection 2020.

DOI:10.3389/fonc.2020.539805
PMID:33072570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7538708/
Abstract

OBJECTIVE

To investigate the role of lncRNA-BLACAT1 in promoting H3K27 trimethylation of CDKN1C gene by recruiting EZH2 to regulate CCNE on glycolysis and mitochondrial oxidative phosphorylation of pancreatic cancer (PC) cells.

METHODS

Following bioinformatic prediction, EZH2 and BLACAT1 in PC cells were interfered, and cells proliferation, migration and invasion in each group were detected. Western blotting detected the expression of key proteins of mitochondrial complex. The sub-cellular localization of BLACAT1 was tested, followed by testing the binding of CDKN1C and BLACAT1 with EZH2, followed by verification.

RESULTS

Based on bioinformatic prediction, EZH2 and BLACAT1 were highly expressed in PC, while CDKN1C was lowly expressed (all < 0.05). Interference with EZH2 and BLACAT1 inhibited cell proliferation, migration and aerobic glycolysis, and promoted mitochondrial oxidative phosphorylation (all < 0.05). BLACAT1 promoted H3K27 trimethylation of CDKN1C through recruiting EZH2 (all < 0.05). results showed that BLACAT1 interference inhibited tumor formation (all < 0.05).

CONCLUSION

Interference with BLACAT1 inhibits H3K27 trimethylation of CDKN1C gene by blocking EZH2 recruitment to promote CDKN1C expression and inhibit CCNE expression, thus suppressing PC cell proliferation, migration and aerobic glycolysis, and promoting mitochondrial oxidative phosphorylation.

摘要

目的

探讨长链非编码RNA-BLACAT1通过招募EZH2促进CDKN1C基因H3K27三甲基化，从而调控CCNE对胰腺癌（PC）细胞糖酵解和线粒体氧化磷酸化的作用。

方法

经过生物信息学预测后，干扰PC细胞中的EZH2和BLACAT1，检测各组细胞的增殖、迁移和侵袭情况。蛋白质印迹法检测线粒体复合物关键蛋白的表达。检测BLACAT1的亚细胞定位，随后检测CDKN1C和BLACAT1与EZH2的结合情况，接着进行验证。

结果

基于生物信息学预测，EZH2和BLACAT1在PC中高表达，而CDKN1C低表达（均<0.05）。干扰EZH2和BLACAT1可抑制细胞增殖、迁移及有氧糖酵解，并促进线粒体氧化磷酸化（均<0.05）。BLACAT1通过招募EZH2促进CDKN1C的H3K27三甲基化（均<0.05）。结果显示干扰BLACAT1可抑制肿瘤形成（均<0.05）。

结论

干扰BLACAT1可通过阻断EZH2的招募来抑制CDKN1C基因的H3K27三甲基化，从而促进CDKN1C表达并抑制CCNE表达，进而抑制PC细胞的增殖、迁移及有氧糖酵解，并促进线粒体氧化磷酸化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/38c24e365e4f/fonc-10-539805-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/d95a7c9a879d/fonc-10-539805-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/b1f8e904cc17/fonc-10-539805-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/a07c84a17deb/fonc-10-539805-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/2dd35686118b/fonc-10-539805-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/f164c2539cea/fonc-10-539805-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/0f14e0196e24/fonc-10-539805-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/e0594066d0a3/fonc-10-539805-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/a235cd11b446/fonc-10-539805-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/38c24e365e4f/fonc-10-539805-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/d95a7c9a879d/fonc-10-539805-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/b1f8e904cc17/fonc-10-539805-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/a07c84a17deb/fonc-10-539805-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/2dd35686118b/fonc-10-539805-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/f164c2539cea/fonc-10-539805-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/0f14e0196e24/fonc-10-539805-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/e0594066d0a3/fonc-10-539805-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/a235cd11b446/fonc-10-539805-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b8/7538708/38c24e365e4f/fonc-10-539805-g009.jpg

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