LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis

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.

Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa‐miR‐23b‐3p/KCND2 axis

“…Growing evidence has exposed that lncRNAs and miRNAs are implicated with multiple cancers including cell growth, survival, differentiation, cell cycle, apoptosis, invasion, and metastasis 10–13 . LncRNAs and miRNAs have also been found to play a regulatory role in the growth, metastasis and progression of ICC, such as lncRNA MNX1‐AS1, 14 lncRNA CCAT1, 15 and lncRNA SNHG3 16 . The previous study showed that lncRNA FAM66C promotes proliferation via the inhibition of the proteasomal pathway in prostate cancer 17 .…”

LncRNA MNX1-AS1 promotes ovarian cancer process via targeting the miR-744-5p/SOX12 axis

“…LncRNA MNX1-AS1 is an antisense RNA of motor neuron and pancreas homeobox protein 1 (MNX1) gene. It has been reported that MNX1-AS1, as an oncogene, promotes the development of many cancers, including intrahepatic cholangiocarcinoma, cervical cancer, lung cancer and hepatocellular carcinoma [ 14 – 17 ]. In OC, Li et al confirmed that MNX1-AS1 expression is increased in tumor tissues than matched normal tissues, and overexpression of MNX1-AS1 is associated with poor clinical outcomes [ 18 ].…”

Clinical significance of long noncoding RNA MNX1-AS1 in human cancers: a meta-analysis of cohort studies and bioinformatics analysis based on TCGA datasets

“…Besides, Wu et al [ 24 ] suggested that MNX1-AS1 could enhance tumor cell epithelial-mesenchymal transition through upregulating MNX1 expression. Autologously, Li et al uncovered that MNX1-AS1 could also enhance MNX1 transcription, which then activated Ajuba/Hippo signaling pathway in intrahepatic cholangiocarcinoma cells, consequently facilitating tumor progression [ 13 ]. In esophagus cancer, MNX1-AS1 was also demonstrated to facilitate the proliferative and invasive capacities of tumor cells through regulating the miR-34a/SIRT1 signaling axis [ 14 ].…”

“…MNX1 antisense RNA 1 (MNX1-AS1) was firstly discovered as a highly expressed gene in colorectal malignant tumor, which is termed CCAT5 as well [12]. Recently, a growing number of studies suggested that MNX1-AS1 was aberrantly expressed in diverse malignancies, including cholangiocarcinoma [13], esophagus cancer [14], breast carcinoma [15][16][17], gastric carcinoma [12,18,19], bladder carcinoma [20], ovarian carcinoma [21,22], cervical cancer [23], osteosarcoma [24,25], laryngeal cancer [26], lung cancer [27][28][29], prostate cancer [30], hepatocellular carcinoma [15], glioblastoma [31] and colon adenocarcinoma [32]. Moreover, aberrant MNX1-AS1 expression has been proposed to correlated with cancer patient survival, indicating its potential as prognostic marker and therapeutic target [12,15,18,23,26].…”