scholarly journals Long noncoding RNA HULC accelerates the growth of human liver cancer stem cells by upregulating CyclinD1 through miR675-PKM2 pathway via autophagy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chen Wang ◽  
Xiaoxue Jiang ◽  
Xiaonan Li ◽  
Shuting Song ◽  
Qiuyu Meng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Noncoding Rna ◽  
Liver Cancer Stem Cells ◽  
Huh7 Cells ◽  
Human Liver Cancer

Abstract Background The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells. Methods Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed. Results We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells. Conclusions It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

scholarly journals Mutant MEG3 Enhances the Activity of Telomerase by Increasing DNA Damage Repair in Human Liver Cancer Stem Cells

2021 ◽  
Author(s):  
Shuting Song ◽  
Sijie Xie ◽  
Rushi Qin ◽  
Yanan Lu ◽  
Liyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Dna Damage Repair ◽  
Liver Cancer Stem Cells ◽  
Damage Repair ◽  
Human Liver Cancer

Abstract Background: Long noncoding RNAs have recently considered as central regulators in diverse biological processes and emerged as vital players controlling tumorigenesis. Although wild MEG3 acts as a suppressor in several cancers, the function of mutant MEG3 is also unclear during tumorigenesis.Methods: Lentivalus infection,RT-PCR,Western blotting and tumorigenesis test in vitro and in vivo were performed.Results: our results suggest that mutant MEG3 promotes the growth of human liver cancer stem cells in vivo and in vitro.Mechanistically, our results show that mutant MEG3 enhances acetylation modification of HistoneH4 on K16.Then, mutant MEG3 enhances the expression of SETD2 dependent on H4K16Ac.Moreover, mutant MEG3 increases the DNA damage repair through SETD2.Ultimately, mutant MEG3 increases the telomeras activity dependent on DNA damage repair.Strikingly,TERT determines the cancerous function of mutant MEG3 in liver cancer stem cells. Therefore, we shed light on the fact that targeting mutant MEG3 could be a viable approach for cancer treatment.Conclusions: these observations will play an important role in finding effective tumor treatment targets.

MK2206 overcomes the resistance of human liver cancer stem cells to sorafenib by inhibition of pAkt and upregulation of pERK

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8047-8055 ◽  
Author(s):  
Beibei Zhai ◽  
Xiaofeng Zhang ◽  
Bin Sun ◽  
Lu Cao ◽  
Linlin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer

scholarly journals miR24-2 Promotes Malignant Progression of Human Liver Cancer Stem Cells by Enhancing Tyrosine Kinase Src Epigenetically

2020 ◽  
Vol 28 (2) ◽  
pp. 572-586 ◽  
Author(s):  
Liyan Wang ◽  
Xiaonan Li ◽  
Wei Zhang ◽  
Yuxin Yang ◽  
Qiuyu Meng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Tyrosine Kinase ◽  
Human Liver ◽  
Malignant Progression ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer

scholarly journals Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically

2020 ◽  
Author(s):  
Xiaoxue Jiang ◽  
Liyan wang ◽  
sijie xie ◽  
Yingjie Chen ◽  
Shuting Song ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Rna Polymerase Ii ◽  
Human Liver ◽  
Noncoding Rna ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Promoter Regions ◽  
Human Liver Cancer

Abstract Background: MEG3 is abnormally down-regulated in most tumors and inhibits tumorigenesis. Methods: Gene infection, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: MEG3 increased the loading of P300 and RNA polymerase II onto the promoter regions of P53. Notably, MEG3 increased the methylation of histone H3 at lysine 27 through increasing the interplay between PRC2 and histone H3. Furthermore, MEG3 inhibited the expression of TERT by increasing the H3K27me3 and decreasing the loading of RNA pol Ⅱ in TERT promoter regions. Moreover, MEG3 inhibit the activity of telomerase by reducing the binding of TERT to TERC competitively. In addition, MEG3 also increased the TERRA through reducing DNA methyltransferase DNMT3b binding to the promoter regions of TERRA competitively. Therefore, the interaction between TERC and TERT was competitively attenuated by increasing the interaction between TERRA and TERT, which inhibited the activity of telomerase in hLCSCs.In particular, MEG3 shortened the length of telomere by blocking the formation of complex maintaining telomere length(POT1-Exo1-TRF2-SNM1B) and decreasing the binding of the complex to telomere competitively, which was caused by increasing the interplay between P53 and HULC in hLCSCs.Strikingly, MEG3 inhibited the growth in vitro and in vivo of hLCSCs by reducing the activity of telomerase and attenuating telomeric repeat binding factor 2(TRF2). Conclusions: our results demonstrated MEG3 inhibits the occurrence of human liver cancer and these findings provide an important insight into the prevention and treatment of human liver cancer.

scholarly journals Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoxue Jiang ◽  
Liyan Wang ◽  
Sijie Xie ◽  
Yingjie Chen ◽  
Shuting Song ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Rna Polymerase Ii ◽  
Human Liver ◽  
Noncoding Rna ◽  
Telomerase Activity ◽  
Promoter Regions ◽  
P53 Expression ◽  
Human Liver Cancer

Abstract Background MEG3 downregulated the expression in several tumors and inhibits human tumorigenesis. But so far, the mechanism of MEG3 in tumorigenesis is still unclear. Methods In gene infection, cellular and molecular technologies and tumorigenesis test in vitro and in vivo were performed, respectively. Results Our results indicate that MEG3 enhances the P53 expression by triggering the loading of P300 and RNA polymerase II onto its promoter regions dependent on HP1α. Moreover, MEG3 increases the methylation modification of histone H3 at the 27th lysine via P53. Furthermore, MEG3 inhibits the expression of TERT by increasing the H3K27me3 in TERT promoter regions, thereby inhibiting the activity of telomerase by reducing the binding of TERT to TERC. Furthermore, MEG3 also increases the expression of TERRA; therefore, the interaction between TERC and TERT was competitively attenuated by increasing the interaction between TERRA and TERT, which inhibits the activity of telomerase in hLCSCs. Strikingly, MEG3 reduces the length of telomere by blocking the formation of complex maintaining telomere length (POT1-Exo1-TRF2-SNM1B) and decreasing the binding of the complex to telomere by increasing the interplay between P53 and HULC. Ultimately, MEG3 inhibits the growth of hLCSCs by reducing the activity of telomerase and attenuating telomeric repeat binding factor 2(TRF2). Conclusions Our results demonstrates MEG3 inhibits the occurrence of human liver cancer by blocking telomere, and these findings provide an important insight into the prevention and treatment of human liver cancer.

scholarly journals CircMEG3 inhibits telomerase activity by reducing Cbf5 in human liver cancer stem cells

2021 ◽  
Vol 23 ◽  
pp. 310-323
Author(s):  
Xiaoxue Jiang ◽  
Libo Xing ◽  
Yingjie Chen ◽  
Rushi Qin ◽  
Shuting Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Telomerase Activity ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer

scholarly journals COL14A1 promotes self-renewal of human liver cancer stem cells through activation of ERK signaling

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ruijiao Kong ◽  
Haidong Liu ◽  
Yi Shi ◽  
Qiuhong Man ◽  
Shanrong Liu
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Erk Signaling ◽  
Self Renewal ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer
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