title: HULC cooperates with MALAT1 to aggravate liver cancer stem cells growth through telomere repeat-binding factor 2.
abstract: The dysregulation of lncRNAs has increasingly been linked to many human diseases, especially in cancers. Our results demonstrate HULC, MALAT1 and TRF2 are highly expressed in human hepatocellular carcinoma tissues, and HULC plus MALAT1 overexpression drastically promotes the growth of liver cancer stem cells. Mechanistically, both HULC and MALAT1 overexpression enhanced RNA polII, P300, CREPT to load on the promoter region of telomere repeat-binding factor 2(TRF2), triggering the overexpression, phosphorylation and SUMOylation of TRF2. Strikingly, the excessive TRF2 interacts with HULC or MALAT1 to form the complex that loads on the telomeric region, replacing the CST/AAF and recruiting POT1, pPOT1, ExoI, SNM1B, HP1 α. Accordingly, the telomere is greatly protected and enlonged. Furthermore, the excessive HULC plus MALAT1 reduced the methylation of the TERC promoter dependent on TRF2, increasing the TERC expression that causes the increase of interplay between TRET and TERC. Ultimately, the interaction between RFC and PCNA or between CDK2 and CyclinE, the telomerase activity and the microsatellite instability (MSI) are significantly increased in the liver cancer stem cells. Our demonstrations suggest that haploinsufficiency of HULC/MALAT1 plays an important role in malignant growth of liver cancer stem cell.
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Mengying
authors: M
authors: Wu
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Zhuojia
authors: Z
authors: Lin
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Xiaonan
authors: X
authors: Li
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Xiaoru
authors: X
authors: Xin
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Jiahui
authors: J
authors: An
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Qidi
authors: Q
authors: Zheng
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Yuxin
authors: Y
authors: Yang
authors: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors: Dongdong
authors: D
authors: Lu
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C574685:HULC long non-coding RNA, human; C557041:MALAT1 long non-coding RNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2