Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA–MUF Interaction with ANXA2 and miR-34a

Abstract

Accumulating evidence suggests that cancer-associated mesenchymal stem cells (MSC) contribute to the development and metastasis of hepatocellular carcinoma (HCC). Aberrant expression of long noncoding RNAs (lncRNA) has been associated with these processes but cellular mechanisms are obscure. In this study, we report that HCC-associated mesenchymal stem cells (HCC-MSC) promote epithelial-mesenchymal transition (EMT) and liver tumorigenesis. We identified a novel lncRNA that we termed (MSC-upregulated factor) that is highly expressed in HCC tissues and correlated with poor prognosis. Depleting in HCC cells repressed EMT and inhibited their tumorigenic potential. Conversely, lncRNA-MUF overexpression accelerated EMT and malignant capacity. Mechanistic investigations showed that bound Annexin A2 (ANXA2) and activated Wnt/β-catenin signaling and EMT. Furthermore, lncRNA-MUF acted as a competing endogenous RNA for miR-34a, leading to Snail1 upregulation and EMT activation. Collectively, our findings establish a lncRNA-mediated process in MSC that facilitates hepatocarcinogenesis, with potential implications for therapeutic targeting..

Downregulation of long non‐coding RNA Opa interacting protein 5‐antisense RNA 1 inhibits breast cancer progression by targeting sex‐determining region Y‐box 2 by microRNA‐129‐5p upregulation

“…The functional role of a lncRNA depends on the downstream molecules that it regulates, including the miRNAs it affects in its function as a ceRNA. The lncRNA mesenchymal stem cells‐upregulated factor (MUF) functions as a ceRNA of miR‐34a to regulate Snail1 activity and modulate hepatocellular carcinoma (HCC) progression . The lncRNA HOXD‐AS1 is upregulated in HCC tissues and competitively binds miR‐130a‐3p, regulating EZH2 and MMP2 expression and facilitating HCC metastasis .…”

“…The lncRNA mesenchymal stem cells-upregulated factor (MUF) functions as a ceRNA of miR-34a to regulate Snail1 activity and modulate hepatocellular carcinoma (HCC) progression. 29 The lncRNA HOXD-AS1 is upregulated in HCC tissues and competitively binds miR-130a-3p, regulating EZH2 and MMP2 expression and facilitating HCC metastasis. 30 By online software prediction, we found the possibility of the existence of the OIP5-AS1/miR-129-5p/ SOX2 axis.…”

Systematic identification of lincRNA‐based prognostic biomarkers by integrating lincRNA expression and copy number variation in lung adenocarcinoma

“…We identified a known lung cancer‐related lincRNA LINC00941 and four novel lincRNA‐based prognostic biomarkers, namely, LINC00578 , TDRKH‐AS1, RBPMS‐AS1 and RP11‐470 M17.2 in LUAD patient samples. LINC00941 was reported to promote mesenchymal stem cells to hepatocarcinogenesis, whose high expression in LUAD was associated with poorer OS of LUAD patients (FDR = 7.7e‐07). The association between LINC00941 and lung cancer was supported by previous findings that LINC00941 act as a robust prognostic classifier in stage I LUAD patients.…”

Glutamine synthetase promotes tumor invasion in hepatocellular carcinoma through mediating epithelial–mesenchymal transition

“…GS is a target of the Wnt/beta‐catenin signal pathway in the liver, and the expression of GS is regulated by translocation of beta‐catenin from the cytoplasm to the cell nucleus, which indicates the activation of the Wnt/beta‐catenin signal pathway . Recently, studies have shown that activation of this pathway contributes to carcinogenesis and epithelial–mesenchymal transition (EMT) in HCC . Therefore, it is logical to speculate that GS might play a critical role in HCC progression.…”