Abstract
Long non-coding RNAs (lncRNAs) have extremely complex roles in the progression of intrahepatic cholangiocarcinoma (ICC) and remain to be elucidated. By cytological and animal model experiments, this study demonstrated that the expression of lncRNA MNX1-AS1 was remarkably elevated in ICC cell lines and tissues, and was highly and positively correlated with motor neuron and pancreas homeobox protein 1 (MNX1) expression. MNX1-AS1 significantly facilitated the proliferation, migration, invasion, and angiogenesis in ICC cells in vitro, and remarkably promoted tumor growth and metastasis in vivo. Further study revealed that MNX1-AS1 promoted the expression of MNX1 via recruiting transcription factors c-Myc and myc-associated zinc finger protein (MAZ). Furthermore, MNX1 upregulated the expression of Ajuba protein via binding to its promoter region, and subsequently, Ajuba protein suppressed the Hippo signaling pathway. Taken together, our results uncovered that MNX1-AS1 can facilitate ICC progression via MNX1-AS1/c-Myc and MAZ/MNX1/Ajuba/Hippo pathway, suggesting that MNX1-AS1 may be able to serve as a potential target for ICC treatment.
Highlights
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma (HCC)
We investigated the location of motor neuron and pancreas homeobox protein 1 (MNX1)-AS1 in cholangiocarcinoma cells via Fluorescence in situ hybridization (FISH) assay which showed that MNX1-AS1 mainly existed in the nucleus of the RBE and FRH0201 cell lines (Fig. 1h), indicating that it mainly had roles in the nucleus
These results demonstrated that the expressions of MNX1-AS1 and MNX1 were highly expressed in ICC tissues and cell lines, and the expression levels of the two genes were highly and positively correlated to each other
Summary
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma (HCC). In the last few decades, the incidence of ICC has been rising in both Eastern and Western countries paralleled by an increase in ICC-related mortality[1]. ICC has high malignancy, and surgical resection is currently the only widely accepted curative treatment[2]. It is difficult to diagnose at an early stage, leading to a loss of opportunity for surgery. Because of the high recurrence rate after surgical resection, the 5-year survival rate of ICC is only 15–40%3.
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