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长链非编码RNA LGALS8-AS1通过miR-125b-5p/SOX12反馈调节网络促进乳腺癌转移。

LncRNA LGALS8-AS1 Promotes Breast Cancer Metastasis Through miR-125b-5p/SOX12 Feedback Regulatory Network.

作者信息

Zhai Duanyang, Li Tianfu, Ye Runyi, Bi Jiong, Kuang Xiaying, Shi Yawei, Shao Nan, Lin Ying

机构信息

Breast Disease Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Oncol. 2021 Oct 22;11:711684. doi: 10.3389/fonc.2021.711684. eCollection 2021.

Abstract

BACKGROUND

Metastasis is a major factor weakening the long-term survival of breast cancer patients. Increasing evidence revealed that long non-coding RNAs (lncRNAs) were involved in the occurrence and development of breast cancer. In this study, we aimed to investigate the role of LGALS8-AS1 in the metastatic progression of breast cancer cells and its potential mechanisms.

RESULTS

The lncRNA LGALS8-AS1 was highly expressed in breast cancer and associated with poor survival. LGALS8-AS1 functioned as an oncogenic lncRNA that promoted the metastasis of breast cancer both and . It upregulated SOX12 competing as a competing endogenous RNA (ceRNA) for sponging miR-125b-5p and acted on the PI3K/AKT signaling pathway to promote the metastasis of breast cancer. Furthermore, SOX12, in turn, activated LGALS8-AS1 expression direct recognition of its sequence binding enrichment motif on the LGALS8-AS1 promoter, thereby forming a positive feedback regulatory loop.

CONCLUSION

This study manifested a novel mechanism of LGALS8-AS1 facilitating the metastasis of breast cancer. The LGALS8-AS1/miR-125b-5p/SOX12 reciprocal regulatory loop dyscrasia promoted the migration and invasion of breast cancer cells. This signaling axis could be applicable to the design of novel therapeutic strategies against this malignancy.

摘要

背景

转移是削弱乳腺癌患者长期生存的主要因素。越来越多的证据表明,长链非编码RNA(lncRNA)参与了乳腺癌的发生和发展。在本研究中,我们旨在探讨LGALS8-AS1在乳腺癌细胞转移进程中的作用及其潜在机制。

结果

lncRNA LGALS8-AS1在乳腺癌中高表达,且与不良生存相关。LGALS8-AS1作为一种致癌lncRNA,促进了乳腺癌的转移。它通过作为竞争性内源RNA(ceRNA)与miR-125b-5p结合来上调SOX12,并作用于PI3K/AKT信号通路以促进乳腺癌转移。此外,SOX12通过直接识别LGALS8-AS1启动子上其序列结合富集基序,反过来激活LGALS8-AS1的表达,从而形成一个正反馈调节环。

结论

本研究揭示了LGALS8-AS1促进乳腺癌转移的新机制。LGALS8-AS1/miR-125b-5p/SOX12相互调节环失调促进了乳腺癌细胞的迁移和侵袭。该信号轴可应用于针对这种恶性肿瘤的新型治疗策略的设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603d/8570098/7f67583ac25c/fonc-11-711684-g001.jpg

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