LncRNA HABON promoted liver cancer cells survival under hypoxia by inhibiting mPTP opening

Hypoxia is an important feature of the tumor microenvironment (TME). While targeting hypoxic TME is emerging as a potential strategy for treating solid tumors including liver cancer. Recent studies have shown that hypoxia can regulate tumor adaptation to hypoxic TME through long non-coding RNA (lncR...

Full description

Bibliographic Details
Main Authors: Gong, X. (Author), He, M. (Author), Hu, Z. (Author), Li, J. (Author), Ma, C. (Author), Wo, L. (Author), Zhan, M. (Author), Zhang, X. (Author), Zhao, Q. (Author), Zhou, C. (Author)
Format: Article
Language:English
Published: Springer Nature 2022
Online Access:View Fulltext in Publisher
LEADER 02440nam a2200241Ia 4500
001 10-1038-s41420-022-00917-6
008 220425s2022 CNT 000 0 und d
020 |a 20587716 (ISSN) 
245 1 0 |a LncRNA HABON promoted liver cancer cells survival under hypoxia by inhibiting mPTP opening 
260 0 |b Springer Nature  |c 2022 
856 |z View Fulltext in Publisher  |u https://doi.org/10.1038/s41420-022-00917-6 
520 3 |a Hypoxia is an important feature of the tumor microenvironment (TME). While targeting hypoxic TME is emerging as a potential strategy for treating solid tumors including liver cancer. Recent studies have shown that hypoxia can regulate tumor adaptation to hypoxic TME through long non-coding RNA (lncRNA). In the previous study, we identify a novel hypoxia-activated lncRNA and termed it as HABON. Here, we demonstrated that knockdown of HABON caused necroptosis of tumor tissue and inhibited the subcutaneous tumor growth of SMMC-7721 cells in nude mice. Moreover, knockdown of HABON increased RIPK1 and MLKL expression as well as their phosphorylation level in SMMC-7721 and Huh7 liver cancer cells. Meanwhile, Necrostatin-1 and GSK872 could restore cell death of liver cancer cells caused by knockdown of HABON under hypoxia. The above results suggested that HABON could inhibit hypoxia-induced necroptosis of liver cancer cells. Mechanically, knockdown of HABON in liver cancer cells aggravated mitochondrial dysfunction caused by hypoxia. Furthermore, the RNA pull-down combined with mass spectrometry analysis identified HABON can interact with mitochondria-related protein VDAC1 and the RNA immunoprecipitation (RIP) analysis proved the interaction. In addition, we proved that VDAC1 mediated the mitochondrial permeability transition pore (mPTP) opening, mitochondrial dysfunction, as well as necroptosis caused by knockdown of HABON. Overall, our work demonstrates HABON can reduce hypoxia-induced necroptosis of liver cancer cells and suggests that inhibition of HABON in the hypoxic TME is a potential therapeutic strategy for treating liver cancer. © 2022, The Author(s). 
700 1 |a Gong, X.  |e author 
700 1 |a He, M.  |e author 
700 1 |a Hu, Z.  |e author 
700 1 |a Li, J.  |e author 
700 1 |a Ma, C.  |e author 
700 1 |a Wo, L.  |e author 
700 1 |a Zhan, M.  |e author 
700 1 |a Zhang, X.  |e author 
700 1 |a Zhao, Q.  |e author 
700 1 |a Zhou, C.  |e author 
773 |t Cell Death Discovery