Inflammatory cytokine IL6 cooperates with CUDR to aggravate hepatocyte-like stem cells malignant transformation through NF-κB signaling.
Inflammatory cytokines and lncRNAs are closely associated with tumorigenesis. Herein, we reveal inflammatory cytokines IL6 cooperates with long noncoding RNA CUDR to trigger the malignant transformation of human embryonic stem cells-derived hepatocyte-like stem cells. Mechanistically, IL6 cooperates with CUDR to cause MELLT3 to interact with SUV39h1 mRNA3'UTR and promote SUV39h1 expression. Moreover, the excessive SUV39h1 also increases tri-methylation of histone H3 on nineth lysine (H3K9me3). Intriguingly, under inflammatory conditions, H3K9me3 promotes the excessive expression and phosphorylation of NF-κB, and in turn, phorsphorylated NF-κB promotes the expression and phosphorylation of Stat3. Furthermore, that the phosphorylated Stat3 loads onto the promoter region of miRs and lncRNAs. Ultimately, the abnormal expression of miRs and lncRNAs increased telomerase activity, telomere length and microsatellite instability (MSI), leading to malignant transformation of hepatocyte-like stem cells.
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Qidi
Q
Zheng
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Zhuojia
Z
Lin
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Xiaonan
X
Li
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Xiaoru
X
Xin
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Mengying
M
Wu
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Jiahui
J
An
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Xin
X
Gui
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Tianming
T
Li
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Hu
H
Pu
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Haiyan
H
Li
School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
Dongdong
D
Lu
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008780:Methyltransferases / Q000378:metabolism; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism; D053842:Microsatellite Instability; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D059505:Telomere Homeostasis
C508600:IL6 protein, human; D015850:Interleukin-6; D035683:MicroRNAs; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C515159:UCA1 RNA, human; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C515701:SUV39H2 protein, human; D019098:Telomerase