A novel regulatory loop miR-101/ANXA2/EGR1 mediates malignant characteristics of liver cancer stem cells

Author:

Ma Sai1,Cheng Junping2,Wang Haiyan2,Ding Ningling2,Zhou Feng2,Ji Runing1,Zhu Li2,Zhu Chuanwu2,Pan Yunzhi2

Affiliation:

1. Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu Province, China

2. Department of Pharmacy, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu Province, China

Abstract

Abstract Increasing evidence suggests that liver cancer stem cells (LCSCs) are the cellular determinants that promote tumor recurrence and metastases. Aberrantly expressed miRNAs were identified in LCSCs and found to play a significant role in modulating biological characteristics of LCSCs. In this study, we implemented miRNA microarrays in CD133+ LCSCs and found miR-101 expression was downregulated. Increasing miR-101 expression repressed the metastasis and tumorigenic potential in LCSCs. Further investigations showed that ANXA2 was a novel target of miR-101. And we revealed that ANXA2 plays a critical role in acceleration of cell cycle and enhancing the migration and invasion abilities of LCSCs. Elevated ANXA2 increased activation of extracellular signal-regulated kinase (ERK) which regulated SOX2 and cell cycle-related kinases. Moreover, ERK phosphorylation inhibited the expression of early growth response 1 (EGR1) which in turn restrained the transcription of miR-101. In vivo experiments, overexpression of miR-101 produced potent inhibitory effects on the growth of LCSCs xenograft tumors as well as ANXA2 knockdown. Taken together, our findings suggest a novel regulatory loop miR-101/ANXA2/EGR1 in LCSCs and may serve as potential therapeutic targets in liver cancer.

Funder

Project of Invigorating Health Care through Science and Education

Health Talent Training Project of Suzhou

Natural Science Foundation of Jiangsu Province

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

Reference39 articles.

1. Cancer statistics, 2020;Siegel;CA Cancer J. Clin.,2020

2. Microenvironmental regulation of tumor progression and metastasis;Quail;Nat. Med.,2013

3. Liver cancer stem cells;Sell;J. Clin. Oncol.,2008

4. Unravelling cancer stem cell potential;Beck;Nat. Rev. Cancer,2013

5. Cancer stem cells revisited;Batlle;Nat. Med.,2017

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