Tumor-associated mesenchymal stem cells promote hepatocellular carcinoma metastasis via a DNM3OS/KDM6B/TIAM1 axis. (10th April 2021)

• Record Type: Journal Article
• Authors: Wang, Wei; Wang, Qun; Huang, Da-Bing; Sun, Qi-Kai; Wu, Shu-Sheng; Zhao, Ya-Jun; Jia, Wei; Hu, De-Sheng; He, Yi-Fu
• Is Part Of: Cancer letters. Volume 503(2021)
• Page Start: 19
• Page End: 31
• Publication Date: 2021-04-10
• Subjects: Hepatocellular carcinoma -- DNM3OS -- KDM6B -- Mesenchymal stem cells; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.01.011
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Tumor-associated mesenchymal stem cells (MSCs) play a critical role in the growth and metastasis of hepatocellular carcinoma (HCC). However, the mechanism underlying the crosstalk between MSCs and HCC cells is not completely understood. Here, HCC cells were treated with or without conditioned medium of MSCs (CM-MSC), and examined for differential expression of long non-coding RNAs (lncRNAs). Knockdown and overexpression experiments were conducted to explore the function of the lncRNA DNM3OS in MSC-induced HCC growth and metastasis. CM-MSC treatment led to a concentration-dependent induction of DNM3OS in HCC cells. DNM3OS was significantly upregulated in HCC compared to adjacent liver tissues. High DNM3OS expression was associated with TNM stage, vascular invasion, and poor prognosis of HCC patients. Silencing of DNM3OS inhibited HCC cell proliferation and invasion in vitro and tumorigenesis and metastasis in vivo . Overexpression of DNM3OS enhanced HCC cell proliferation, invasion, and metastasis. Biochemically, DNM3O S was mainly localized in the nucleus and physically interacted with KDM6B. The association of DNM3OS with KDM6B induced the expression of TIAM1 through reduction of H3K27me3 at the TIAM1 promoter. TIAM1 overexpression restored the proliferation and invasion of DNM3OS -depleted HCC cells. Our data delineate a mechanism by which MSCs accelerate HCC growth and metastasis through a DNM3OS /KDM6B/TIAM1 axis. Highlights: DNM3OS is upregulated in HCC cells by mesenchymal stem cells. DNM3OS promotes HCC cell tumorigenesis and metastasis. DNM3OS physically interacts with KDM6B. DNM3OS leads to a reduction of H3K27me3 at the TIAM1 promoter.