Long non-coding RNA HOTAIR up-regulates chemokine (C-C motif) ligand 2 and promotes proliferation of macrophages and myeloid-derived suppressor cells in hepatocellular carcinoma cell lines

长链非编码 RNA HOTAIR 上调趋化因子 (CC 基序) 配体 2 并促进肝细胞癌细胞系中巨噬细胞和髓系抑制细胞的增殖

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作者:Yasuyuki Fujisaka, Tomoaki Iwata, Keiichi Tamai, Mao Nakamura, Mai Mochizuki, Rie Shibuya, Kazunori Yamaguchi, Tooru Shimosegawa, Kennichi Satoh

Abstract

Accumulating evidence demonstrated that Hox antisense intergenic RNA (HOTAIR) serves essential roles in the development and metastasis of several types of cancer. In hepatocellular carcinoma (HCC), high expression of HOTAIR is associated with poor prognosis, and HOTAIR regulates cell migration and proliferation. However, the downstream molecular targets of HOTAIR depend on the cancer cell types, and little is known about the precise molecular mechanisms of HOTAIR involved in cancer development. The present study investigated the role of HOTAIR in HCC cell lines. Notably, the overexpression of HOTAIR in HCC cell lines did not affect cell migration and proliferation capability. In the microarray analysis, C-C motif chemokine ligand (CCL)2 was identified to be differentially expressed in HOTAIR-overexpressing cells, and it was confirmed that HOTAIR promotes the secretion of CCL2. Furthermore, it was revealed that the proportion of macrophages and myeloid-derived suppressor cells (MDSCs) were increased when peripheral blood mononuclear cells were co-cultured with HOTAIR-overexpressing cells. Collectively, these data suggest that HOTAIR regulates CCL2 expression, which may be involved in the recruitment of macrophages and MDSCs to the tumor microenvironment.

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