Dysregulated cholesterol regulatory genes in hepatocellular carcinoma

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

Article  PubMed  Google Scholar 

Luo J, Yang H, Song B-L. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21:225–45.

Article  CAS  PubMed  Google Scholar 

Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1:31–9.

Article  CAS  PubMed  Google Scholar 

Javitt NB. Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB J. 1994;8:1308–11.

Article  CAS  PubMed  Google Scholar 

Göbel A, Rauner M, Hofbauer LC, Rachner TD. Cholesterol and beyond: the role of the mevalonate pathway in cancer biology. Biochim Biophys Acta Rev Cancer. 2020;1873: 188351.

Article  PubMed  Google Scholar 

Xu H, Zhou S, Tang Q, Xia H, Bi F. Cholesterol metabolism: new functions and therapeutic approaches in cancer. Biochim Biophys Acta Rev Cancer. 2020;1874: 188394.

Article  CAS  PubMed  Google Scholar 

Bhattacharjee P, Rutland N, Iyer MR. Targeting sterol O-acyltransferase/Acyl-CoA: cholesterol acyltransferase (ACAT): a perspective on small-molecule inhibitors and their therapeutic potential. J Med Chem. 2022;65:16062–98.

Article  CAS  PubMed  Google Scholar 

Wang L-J, Song B-L. Niemann-Pick C1-like 1 and cholesterol uptake. Biochim Biophys Acta. 2012;1821:964–72.

Article  CAS  PubMed  Google Scholar 

Kober DL, Xu S, Li S, Bajaj B, Liang G, Rosenbaum DM, et al. Identification of a degradation signal at the carboxy terminus of SREBP2: a new role for this domain in cholesterol homeostasis. Proc Natl Acad Sci USA. 2020;117:28080–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kuzu OF, Gowda R, Noory MA, Robertson GP. Modulating cancer cell survival by targeting intracellular cholesterol transport. Br J Cancer. 2017;117:513–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

He J, Siu MKY, Ngan HYS, Chan KKL. Aberrant cholesterol metabolism in ovarian cancer: identification of novel therapeutic targets. Front Oncol. 2021;11: 738177.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alannan M, Trézéguet V, Amoêdo ND, Rossignol R, Mahfouf W, Rezvani HR, et al. Rewiring lipid metabolism by targeting PCSK9 and HMGCR to treat liver cancer. Cancers. 2022;15:3.

Article  PubMed  PubMed Central  Google Scholar 

Liang B, Chen R, Song S, Wang H, Sun G, Yang H, et al. ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma. Cell Death Dis. 2019;10:830.

Article  PubMed  PubMed Central  Google Scholar 

Cao Z, Fan-Minogue H, Bellovin DI, Yevtodiyenko A, Arzeno J, Yang Q, et al. MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma are regulated by HMG-CoA reductase. Can Res. 2011;71:2286–97.

Article  CAS  Google Scholar 

Dong L, Xue L, Zhang C, Li H, Cai Z, Guo R. HSP90 interacts with HMGCR and promotes the progression of hepatocellular carcinoma. Mol Med Rep. 2018;19:524–32.

PubMed  Google Scholar 

Ogura S, Yoshida Y, Kurahashi T, Egawa M, Furuta K, Kiso S, et al. Targeting the mevalonate pathway is a novel therapeutic approach to inhibit oncogenic FoxM1 transcription factor in human hepatocellular carcinoma. Oncotarget. 2018;9:21022–35.

Article  PubMed  PubMed Central  Google Scholar 

Cheng J, Ohsaki Y, Tauchi-Sato K, Fujita A, Fujimoto T. Cholesterol depletion induces autophagy. Biochem Biophys Res Commun. 2006;351:246–52.

Article  CAS  PubMed  Google Scholar 

Cirmena G, Franceschelli P, Isnaldi E, Ferrando L, De Mariano M, Ballestrero A, et al. Squalene epoxidase as a promising metabolic target in cancer treatment. Cancer Lett. 2018;425:13–20.

Article  CAS  PubMed  Google Scholar 

Liu D, Wong CC, Fu L, Chen H, Zhao L, Li C, et al. Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target. Sci Transl Med. 2018;10:eaap9840.

Article  PubMed  Google Scholar 

Shen T, Lu Y, Zhang Q. High squalene epoxidase in tumors predicts worse survival in patients with hepatocellular carcinoma: integrated bioinformatic analysis on NAFLD and HCC. Cancer Control. 2020;27:107327482091466.

Article  Google Scholar 

Zhao K, Zhao Y, Zhu J, Dong H, Cong W, Yu Y, et al. A panel of genes identified as targets for 8q24.13–24.3 gain contributing to unfavorable overall survival in patients with hepatocellular carcinoma. Curr Med Sci. 2018;38:590–6.

Article  CAS  PubMed  Google Scholar 

Sun H, Li L, Li W, Yang F, Zhang Z, Liu Z, et al. p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth. EMBO Rep. 2021;22:525–37.

Article  Google Scholar 

Zhang Z, Wu W, Jiao H, Chen Y, Ji X, Cao J, et al. Squalene epoxidase promotes hepatocellular carcinoma development by activating STRAP transcription and TGF-β/SMAD signalling. Br J Pharmacol. 2023;180:1562–81.

Article  CAS  PubMed  Google Scholar 

Moon S-H, Huang C-H, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JP, et al. p53 represses the mevalonate pathway to mediate tumor suppression. Cell. 2019;176:564–80.

Article  CAS  PubMed  Google Scholar 

Che L, Chi W, Qiao Y, Zhang J, Song X, Liu Y, et al. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut. 2020;69:177–86.

Article  CAS  PubMed  Google Scholar 

Zhang F, Gao J, Liu X, Sun Y, Liu L, Hu B, et al. LATS-regulated nuclear-cytoplasmic translocation of SREBP2 inhibits hepatocellular carcinoma cell migration and invasion via Epithelial–mesenchymal transition. Mol Carcinog. 2023;62:963–74.

Article  CAS  PubMed  Google Scholar 

Wei M, Nurjanah U, Herkilini A, Huang C, Li Y, Miyagishi M, et al. Unspliced XBP1 contributes to cholesterol biosynthesis and tumorigenesis by stabilizing SREBP2 in hepatocellular carcinoma. Cell Mol Life Sci. 2022;79:472.

Article  CAS  PubMed  Google Scholar 

Chen K-J, Jin R-M, Shi C-C, Ge R-L, Hu L, Zou Q-F, et al. The prognostic value of Niemann-Pick C1-like protein 1 and Niemann-Pick disease type C2 in hepatocellular carcinoma. J Cancer. 2018;9:556–63.

Article  PubMed  PubMed Central  Google Scholar 

Barretto N, Sainz B, Hussain S, Uprichard SL. Determining the involvement and therapeutic implications of host cellular factors in hepatitis C virus cell-to-cell spread. J Virol. 2014;88:5050–61.

Article  PubMed  PubMed Central  Google Scholar 

Zhang Z, Qin S, Chen Y, Zhou L, Yang M, Tang Y, et al. Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy. EMBO Mol Med. 2022;14: e14903.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Criscuolo D, Avolio R, Calice G, Laezza C, Paladino S, Navarra G, et al. Cholesterol homeostasis modulates platinum sensitivity in human ovarian cancer. Cells. 2020;9:828.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang G-M, Chen W, Yao Y, Luo L, Sun L-J. LDLR promotes growth and invasion in renal cell carcinoma and activates the EGFR pathway. Neoplasma. 2022;69:113–22.

Article  CAS  PubMed  Google Scholar 

Zeng J, Wu Y, Liao Q, Li L, Chen X, Chen X. Liver X receptors agonists impede hepatitis C virus infection in an Idol-dependent manner. Antiviral Res. 2012;95:245–56.

Article  CAS  PubMed  Google Scholar 

Zhao L-J, Wang L, Ren H, Cao J, Li L, Ke J-S, et al. Hepatitis C virus E2 protein promotes human hepatoma cell proliferation through the MAPK/ERK signaling pathway via cellular receptors. Exp Cell Res. 2005;305:23–32.

Article  CAS  PubMed  Google Scholar 

Bhat M, Skill N, Marcus V, Deschenes M, Tan X, Bouteaud J, et al. Decreased PCSK9 expression in human hepatocellular carcinoma. BMC Gastroenterol. 2015;15:176.

Article  PubMed  PubMed Central  Google Scholar 

Chen Z, Chen L, Sun B, Liu D, He Y, Qi L, et al. LDLR inhibition promotes hepatocellular carcinoma proliferation and metastasis by elevating intracellular cholesterol synthesis through the MEK/ERK signaling pathway. Mol Metab. 2021;51: 101230.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shen S, Wang R, Qiu H, Li C, Wang J, Xue J, et al. Development of an autophagy-based and stemness-correlated prognostic model for hepatocellular carcinoma using bulk and single-cell RNA-sequencing. Front Cell Dev Biol. 2021;9: 743910.

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