Related Experiment Video
Updated: Nov 28, 2025
Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube SWCNT-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
Long noncoding RNA MEG3 blocks telomerase activity in human liver cancer stem cells epigenetically
Xiaoxue Jiang1, Liyan Wang1, Sijie Xie1
1Shanghai Putuo District People's Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.
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.
Insights
The tumor suppressor MEG3 inhibits human tumorigenesis by targeting telomere length and telomerase activity. This research clarifies MEG3
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- The tumor suppressor gene MEG3 is downregulated in various cancers, inhibiting human tumorigenesis.
- The precise molecular mechanisms underlying MEG3's role in tumorigenesis remain largely unelucidated.
Purpose of the Study:
- To investigate the molecular mechanisms by which MEG3 suppresses tumorigenesis.
- To elucidate the role of MEG3 in regulating telomere length and telomerase activity in human liver cancer stem cells (hLCSCs).
Main Methods:
- Gene infection and cellular/molecular technologies were employed.
- In vitro and in vivo tumorigenesis assays were conducted.
- Analysis of protein-DNA interactions and epigenetic modifications was performed.
Main Results:
- MEG3 enhances P53 expression by facilitating P300 and RNA polymerase II loading onto the P53 promoter, dependent on HP1α.
- MEG3 promotes H3K27 trimethylation via P53, inhibiting TERT expression and telomerase activity by disrupting TERT-TERC binding.
- MEG3 reduces telomere length by interfering with telomere maintenance complexes and increasing P53-HULC interplay, ultimately inhibiting hLCSC growth.
Conclusions:
- MEG3 inhibits human liver cancer by targeting telomere length and telomerase activity.
- These findings offer novel insights into the prevention and treatment strategies for human liver cancer.
Related Concept Videos
02:39lncRNA - Long Non-coding RNAs
02:39lncRNA - Long Non-coding RNAs
02:41Telomeres and Telomerase
02:41Telomeres and Telomerase
03:18Non-LTR Retrotransposons
01:22MicroRNAs