Dysregulated cholesterol regulatory genes as a diagnostic biomarker for cancer

被引:15
作者
Kuldeep, Seema [1 ]
Soni, Sneha [1 ]
Srivastava, Anubhav [2 ]
Mishra, Anjali [3 ]
Sharma, Lokendra Kumar [2 ]
Mandal, Chandi C. [1 ,4 ]
机构
[1] Cent Univ Rajasthan, Sch Life Sci, Dept Biochem, Ajmer, Rajasthan, India
[2] Sanjay Gandhi Post Grad Inst Med Sci, Dept Mol Med & Biotechnol, Lucknow, Uttar Pradesh, India
[3] Sanjay Gandhi Post Grad Inst Med Sci, Dept Endocrine & Breast Surg, Lucknow, Uttar Pradesh, India
[4] Cent Univ Rajasthan, Sch Life Sci, Dept Biochem, NH-8, Ajmer 305817, Rajasthan, India
关键词
biomarkers; cancer; cancer therapy; cholesterol; cholesterol regulatory genes; gene signature; COLORECTAL-CANCER; BREAST; SIMVASTATIN; METABOLISM; INHIBITORS; EXPRESSION; SURVIVAL; PATHWAY; DRUGS; RISK;
D O I
10.1002/jgm.3475
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
BackgroundA dysregulation of cholesterol homeostasis is often seen in various cancer cell types, and elevated cholesterol content and that of its metabolites appears to be crucial for cancer progression and metastasis. Cholesterol is a precursor of various steroid hormones and a key plasma membrane component especially in lipid-rafts, also modulating many intracellular signaling pathways. MethodsTo provide an insight of dysregulated cholesterol regulatory genes, their transcript levels were analyzed in different cancers and their influence was correlated with the overall survival of cancer patients using cancer database analysis. ResultsThis analysis found a set of genes (e.g., ACAT1, RXRA, SOAT1 and SQLE) that were not only often dysregulated, but also had been associated with poorer overall survival in most cancer types. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed elevated SQLE and SOAT1 transcript levels and downregulated expression of RXRA and ACAT1 genes in triple negative breast cancer tissues compared to adjacent control tissues, indicating that this dysregulated expression of the gene signature is a diagnostic marker for breast cancer. ConclusionFor the first time, the present study identified a gene signature associated with the dysregulation of cholesterol homeostasis in cancer cells that may not only be used as a diagnostic marker, but also comprise a promising drug target for the advancement of cancer therapy.
引用
收藏
页数:15
相关论文
共 47 条
[1]   N-arachidonoyl dopamine inhibits epithelial-mesenchymal transition of breast cancer cells through ERK signaling and decreasing the cellular cholesterol [J].
Bandyopadhayaya, Shreetama ;
Akimov, Mikhail G. ;
Verma, Ranjeet ;
Sharma, Ankit ;
Sharma, Divya ;
Kundu, Gopal C. ;
Gretskaya, Natalia M. ;
Bezuglov, Vladimir V. ;
Mandal, Chandi C. .
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2021, 35 (04)
[2]   Statin use and cancer risk: a comprehensive review [J].
Boudreau, Denise M. ;
Yu, Onchee ;
Johnson, Jeanene .
EXPERT OPINION ON DRUG SAFETY, 2010, 9 (04) :603-621
[3]   A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
SCIENCE, 1986, 232 (4746) :34-47
[4]   The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].
Cerami, Ethan ;
Gao, Jianjiong ;
Dogrusoz, Ugur ;
Gross, Benjamin E. ;
Sumer, Selcuk Onur ;
Aksoy, Buelent Arman ;
Jacobsen, Anders ;
Byrne, Caitlin J. ;
Heuer, Michael L. ;
Larsson, Erik ;
Antipin, Yevgeniy ;
Reva, Boris ;
Goldberg, Arthur P. ;
Sander, Chris ;
Schultz, Nikolaus .
CANCER DISCOVERY, 2012, 2 (05) :401-404
[5]   UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J].
Chandrashekar, Darshan S. ;
Bashel, Bhuwan ;
Balasubramanya, Sai Akshaya Hodigere ;
Creighton, Chad J. ;
Ponce-Rodriguez, Israel ;
Chakravarthi, Balabhadrapatruni V. S. K. ;
Varambally, Sooryanarayana .
NEOPLASIA, 2017, 19 (08) :649-658
[6]   Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer [J].
Cheema, P. K. ;
Burkes, R. L. .
CURRENT ONCOLOGY, 2013, 20 (02) :E150-E160
[7]   SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Meta-bolic Targets in Cancer Therapy [J].
Cheng, Xiang ;
Li, Jianying ;
Guo, Deliang .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2018, 18 (06) :484-493
[8]   Simvastatin and MBCD Inhibit Breast Cancer-Induced Osteoclast Activity by Targeting Osteoclastogenic Factors [J].
Chowdhury, Kaushik ;
Sharma, Ankit ;
Sharma, Tanu ;
Kumar, Suresh ;
Mandal, Chandi C. .
CANCER INVESTIGATION, 2017, 35 (06) :403-413
[9]  
Croft D, 2014, NUCLEIC ACIDS RES, V42, pD472, DOI [10.1093/nar/gkt1102, 10.1093/nar/gkz1031]
[10]   The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics [J].
Cruz, Pedro M. R. ;
Mo, Huanbiao ;
McConathy, Walter J. ;
Sabnis, Nirupama ;
Lacko, Andras G. .
FRONTIERS IN PHARMACOLOGY, 2013, 4