Long Noncoding RNA SchLAH Suppresses Metastasis of Hepatocellular Carcinoma Through Interacting with Fused in Sarcoma

Overview

Journal Cancer Sci

Specialty Oncology

Date 2017 Feb 15

PMID 28196303

Citations 29

Authors

Zhouhong Ge

Zhuoan Cheng

Xinrong Yang

Xisong Huo

Ning Wang

Hui Wang

Cun Wang

Dishui Gu

Fangyu Zhao

Ming Yao

Jia Fan

Wenxin Qin

Affiliations

Soon will be listed here.

Abstract

Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells. Knockdown of SchLAH by siRNA pool promoted the migration of HCC cells. RNA pull-down and RNA immunoprecipitation assays demonstrated SchLAH physically interacted with fused in sarcoma (FUS). PCR array analysis showed that RhoA and Rac1 were the downstream effector molecules of SchLAH during HCC metastasis. Knockdown of FUS rescued the mRNA levels of RhoA and Rac1 that were repressed by SchLAH. These results suggest that SchLAH may suppress the metastasis of HCC cells by interacting with FUS, which indicates potential of SchLAH for the prognosis and treatment of HCC.

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References

Prensner J, Chinnaiyan A . The emergence of lncRNAs in cancer biology. Cancer Discov. 2011; 1(5):391-407. PMC: 3215093. DOI: 10.1158/2159-8290.CD-11-0209. View

Honda D, Ishigaki S, Iguchi Y, Fujioka Y, Udagawa T, Masuda A . The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons. FEBS Open Bio. 2013; 4:1-10. PMC: 3851184. DOI: 10.1016/j.fob.2013.11.001. View

Lee T, Man K, Ho J, Wang X, Poon R, Sun C . Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target. Carcinogenesis. 2004; 26(3):681-7. DOI: 10.1093/carcin/bgi002. View

Sama R, Ward C, Bosco D . Functions of FUS/TLS from DNA repair to stress response: implications for ALS. ASN Neuro. 2014; 6(4). PMC: 4189536. DOI: 10.1177/1759091414544472. View

Y Tan A, Manley J . The TET family of proteins: functions and roles in disease. J Mol Cell Biol. 2009; 1(2):82-92. PMC: 2905059. DOI: 10.1093/jmcb/mjp025. View

Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S . The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science. 2014; 344(6181):310-3. DOI: 10.1126/science.1251456. View

Cooper T, Wan L, Dreyfuss G . RNA and disease. Cell. 2009; 136(4):777-93. PMC: 2866189. DOI: 10.1016/j.cell.2009.02.011. View

Xing Z, Lin A, Li C, Liang K, Wang S, Liu Y . lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell. 2014; 159(5):1110-1125. PMC: 4266991. DOI: 10.1016/j.cell.2014.10.013. View

Wang X, Arai S, Song X, Reichart D, Du K, Pascual G . Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008; 454(7200):126-30. PMC: 2823488. DOI: 10.1038/nature06992. View

10.

Lagier-Tourenne C, Polymenidou M, Hutt K, Vu A, Baughn M, Huelga S . Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci. 2012; 15(11):1488-97. PMC: 3586380. DOI: 10.1038/nn.3230. View

11.

Wang W, Pan L, Su S, Quinn E, Sasaki M, Jimenez J . Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons. Nat Neurosci. 2013; 16(10):1383-91. PMC: 5564396. DOI: 10.1038/nn.3514. View

12.

Xu D, Yang F, Yuan J, Zhang L, Bi H, Zhou C . Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling. Hepatology. 2013; 58(2):739-51. DOI: 10.1002/hep.26361. View

13.

Diaz-Nunez M, Diez-Torre A, de Wever O, Andrade R, Arluzea J, Silio M . Histone deacetylase inhibitors induce invasion of human melanoma cells in vitro via differential regulation of N-cadherin expression and RhoA activity. BMC Cancer. 2016; 16:667. PMC: 4994393. DOI: 10.1186/s12885-016-2693-3. View

14.

Takayama T . Surgical treatment for hepatocellular carcinoma. Jpn J Clin Oncol. 2011; 41(4):447-54. DOI: 10.1093/jjco/hyr016. View

15.

Aravalli R, Cressman E, Steer C . Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch Toxicol. 2012; 87(2):227-47. DOI: 10.1007/s00204-012-0931-2. View

16.

Forner A, Llovet J, Bruix J . Hepatocellular carcinoma. Lancet. 2012; 379(9822):1245-55. DOI: 10.1016/S0140-6736(11)61347-0. View

17.

Quagliata L, Matter M, Piscuoglio S, Arabi L, Ruiz C, Procino A . Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2013; 59(3):911-23. PMC: 3943759. DOI: 10.1002/hep.26740. View

18.

Zhou C, Yang F, Yuan S, Ma J, Liu F, Yuan J . Systemic genome screening identifies the outcome associated focal loss of long noncoding RNA PRAL in hepatocellular carcinoma. Hepatology. 2015; 63(3):850-63. DOI: 10.1002/hep.28393. View

19.

Cao C, Sun J, Zhang D, Guo X, Xie L, Li X . The long intergenic noncoding RNA UFC1, a target of MicroRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of β-catenin in HCC cells. Gastroenterology. 2014; 148(2):415-26.e18. DOI: 10.1053/j.gastro.2014.10.012. View

20.

Yang F, Zhang L, Huo X, Yuan J, Xu D, Yuan S . Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology. 2011; 54(5):1679-89. DOI: 10.1002/hep.24563. View