Long noncoding RNA HOTAIR promotes metastasis of renal cell carcinoma by up-regulating histone H3K27 demethylase JMJD3.
Long Noncoding RNAs (lncRNAs) are a kind of non-protein coding transcripts longer than 200 nucleotides, and play important roles in diverse biological processes, such as embryonic development and apoptosis. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) is a negative prognostic factor in a variety of human cancers, such as breast, liver and lung cancers. HOTAIR can promote cancer cell metastasis by reprogramming chromatin organization. In the present study, HOTAIR expression was elevated in tissues of renal cell carcinoma compared to adjacent normal tissues, and positively correlated with metastasis (P<0.05). The cell migration was inhibited in scratch test and transwell assay after HOTAIR knockdown (P<0.05). Further researches revealed that histone demethylase JMJD3 was reduced and its target gene Snai1 expression was down-regulated after HOTAIR suppression (P<0.05). Meanwhile, the level of histone methytransferase EZH2 target gene PCDHB5 was increased (P<0.05). Collectively, these data suggest that HOTAIR is an important promoter in metastasis of renal cell carcinoma and also plays a dual regulatory role in chromatin state by effecting both histone metylation and demethylation at different gene loci.
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.|State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.|Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510000, Guangdong, China.
Ming
M
Xia
Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, Guangdong, China.
Lv
L
Yao
State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
Qiaoxia
Q
Zhang
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
Feng
F
Wang
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
Hongbin
H
Mei
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.|State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.|Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei, China.
Xiaoqiang
X
Guo
Department of Urology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.|State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong, China.
Weiren
W
Huang
D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D009362:Neoplasm Metastasis; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C561566:HOTAIR long untranslated RNA, human; D006657:Histones; D062085:RNA, Long Noncoding; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
HOTAIR; JMJD3; histone demethylase; long noncoding RNA; renal cell carcinoma