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

被引:34
作者
Li, Fengwei [1 ]
Chen, Qinjunjie [1 ]
Xue, Hui [2 ]
Zhang, Lei [2 ]
Wang, Kui [2 ]
Shen, Feng [1 ]
机构
[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 4, Shanghai, Peoples R China
[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 2, Shanghai, Peoples R China
关键词
CELL-PROLIFERATION; LIVER RESECTION; NONCODING RNAS; CANCER; INVASION; EXPRESSION; MIGRATION; PROTEINS; OVEREXPRESSION; MANAGEMENT;
D O I
10.1038/s41419-020-03029-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:13
相关论文
共 67 条
[1]   Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma [J].
Bridgewater, John ;
Galle, Peter R. ;
Khan, Shahid A. ;
Llovet, Josep M. ;
Park, Joong-Won ;
Patel, Tushar ;
Pawlik, Timothy M. ;
Gores, Gregory J. .
JOURNAL OF HEPATOLOGY, 2014, 60 (06) :1268-1289
[2]   Emerging roles of long non-coding RNA in cancer [J].
Calle, Anna Sanchez ;
Kawamura, Yumi ;
Yamamoto, Yusuke ;
Takeshita, Fumitaka ;
Ochiya, Takahiro .
CANCER SCIENCE, 2018, 109 (07) :2093-2100
[3]   Motor neuron and pancreas homeobox 1/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1/2 [J].
Chen, Mingkun ;
Wu, Rongpei ;
Li, Gang ;
Liu, Cundong ;
Tan, Lei ;
Xiao, Kanghua ;
Ye, Yunlin ;
Qin, Zike .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37
[4]   C-MYC and BCL-2 mediate YAP-regulated tumorigenesis in OSCC [J].
Chen, Xiyan ;
Gu, Weiting ;
Wang, Qi ;
Fu, Xucheng ;
Wang, Ying ;
Xu, Xin ;
Wen, Yong .
ONCOTARGET, 2018, 9 (01) :668-679
[5]   MNX1-AS1 is a functional oncogene that induces EMT and activates the AKT/mTOR pathway and MNX1 in breast cancer [J].
Cheng, Yue ;
Pan, Yiqi ;
Pan, Yiyuan ;
Wang, Ouchen .
CANCER MANAGEMENT AND RESEARCH, 2019, 11 :803-812
[6]   ZNFX1 anti-sense RNA 1 promotes the tumorigenesis of prostate cancer by regulating c-Myc expression via a regulatory network of competing endogenous RNAs [J].
Cui, Xiaolu ;
Piao, Chiyuan ;
Lv, Chengcheng ;
Lin, Xuyong ;
Zhang, Zhe ;
Liu, Xiankui .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2020, 77 (06) :1135-1152
[7]   Ajuba LIM Proteins Are Negative Regulators of the Hippo Signaling Pathway [J].
Das Thakur, Meghna ;
Feng, Yunfeng ;
Jagannathan, Radhika ;
Seppa, Midori J. ;
Skeath, James B. ;
Longmore, Gregory D. .
CURRENT BIOLOGY, 2010, 20 (07) :657-662
[8]   Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma [J].
Esnaola, Nestor F. ;
Meyer, Joshua E. ;
Karachristos, Andreas ;
Maranki, Jennifer L. ;
Camp, E. Ramsay ;
Denlinger, Crystal S. .
CANCER, 2016, 122 (09) :1349-1369
[9]   The Tumor Suppressor Interferon Regulatory Factor 2 Binding Protein 2 Regulates Hippo Pathway in Liver Cancer by a Feedback Loop in Mice [J].
Feng, Xue ;
Lu, Tiantian ;
Li, Jinhui ;
Yang, Ruizeng ;
Hu, Liqiao ;
Ye, Yi ;
Mao, Feifei ;
He, Lingli ;
Xu, Jinjin ;
Wang, Zuoyun ;
Liu, Yingbin ;
Zhang, Yonglong ;
Ji, Hongbin ;
Zhao, Yun ;
Cheng, Shuqun ;
Tian, Wei ;
Zhang, Lei .
HEPATOLOGY, 2020, 71 (06) :1988-2004
[10]   Non-coding RNAs, epigenetics, and cancer: tying it all together [J].
Ferreira, Humberto J. ;
Esteller, Manel .
CANCER AND METASTASIS REVIEWS, 2018, 37 (01) :55-73