DNAJB5 (hsc40) gene as a novel biomarker for cervical cancer
1Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, 30060 Tianjin, China
2Tianjin Clinical Research Center for Cancer, 30060 Tianjin, China
3Department of Gynaecological Oncology, Tianjin Medical University Cancer Institute and Hospital, 300060 Tianjin, China
4Department of respiratory and critical care medicine, Tianjin Chest Hospital, 300051 Tianjin, China
Submitted: 17 May 2022 Accepted: 13 June 2022
Online publish date: 07 July 2022
Cervical cancer is among the most common malignant tumor and leading cause of cancer-related mortality in women worldwide. Heat shock proteins (HSPs) are reported increasingly as potential biomarkers and drug targets for cancers. DNAJB5 has been shown to be involved in HSP binding and response to unfolded proteins, but its role in cervical cancer remains currently unclear. In this study, DNAJB5 was knocked down in SiHa cells by short hairpin RNA (shRNA) and verified by quantitative real-time polymerase chain reaction (qRT-PCR) as well as Western blotting. Its effects on cell proliferation, apoptosis, viability, and cell cycle were investigated by Celigo assay, Annexin V-Allophycocyanin (Annexin V-APC) assay, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye (MTT) assay and propidium iodide (PI) staining assay, respectively. shRNA experiments successfully knocked down DNAJB5 expression, which decreased the proliferation of SiHa cells, reduced the number of viable cells, affected the cell cycle of SiHa cells and increased their apoptosis. The knockdown of DNAJB5 acted as a tumor suppressor in cervical cancer cells, suggesting DNAJB5 as a new biomarker candidate and potential target for cervical cancer treatment.
DNAJB5; Cervical cancer; shRNA; HSP
Hu Yu,Ying Chen,Guoxin Zhang,Huijuan Wu,Ke Wang. DNAJB5 (hsc40) gene as a novel biomarker for cervical cancer. European Journal of Gynaecological Oncology. 2022.doi:10.22514/ejgo.2022.023.
 Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health. 2020; 8: e191–e203.
 Shrestha AD, Neupane D, Vedsted P, Kallestrup P. Cervical cancer prevalence, incidence and mortality in low and middle income countries: a systematic review. The Asian Pacific Journal of Cancer Prevention. 2018. 19: 319–324.
 Tang D, Khaleque MA, Jones EL, Theriault JR, Li C, Hung Wong W, et al. Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress & Chaperones. 2005; 10: 46.
 Cheng H, Cenciarelli C, Nelkin G, Tsan R, Fan D, Cheng-Mayer C, et al. Molecular mechanism of hTid-1, the human homolog of drosophila tumor suppressor l(2)Tid, in the regulation of NF-B activity and suppression of tumor growth. Molecular and Cellular Biology. 2005. 25: 44–59.
 Kim S, Hayashi M, Lo J, Fearns C, Xiang R, Lazennec G, et al. Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8. Cancer Research. 2005; 65: 8784–8791.
 Kim SW, Chao TH, Xiang R, Lo JF, Campbell MJ, Fearns C, et al. Tid1, the human homologue of a drosophila tumor suppressor, reduces the malignant activity of ErbB-2 in carcinoma cells. Cancer Research. 2004. 64: 7732–7739.
 Copeland E, Balgobin S, Lee CM, Rozakis-Adcock M. HTID-1 defines a novel regulator of c-Met receptor signaling in renal cell carcinomas. Oncogene. 2011; 30: 2252–2263.
 Dhennin-Duthille I, Nyga R, Yahiaoui S, Gouilleux-Gruart V, Régnier A, Lassoued K, et al. The tumor suppressor hTid1 inhibits STAT5b activity via functional interaction. Journal of Biological Chemistry. 2011; 286: 5034–5042.
 Tsai M, Wang C, Chang G, Chen C, Chen H, Cheng C, et al. A new tumor suppressor DNAJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. Journal of the National Cancer Institute. 2006; 98: 825–838.
 Lin S, Hsueh C, Yu S, Su C, Shum W, Yeh K, et al. HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma. Nucleic Acids Research. 2010; 38: 6148–6158.
 Chen C, Lin H, Chuang S, Lin S, Chen JJW. Acidic stress facilitates tyrosine phosphorylation of HLJ1 to associate with actin cytoskeleton in lung cancer cells. Experimental Cell Research. 2010; 316: 2910–2921.
 Mitra A, Menezes ME, Shevde LA, Samant RS. DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype. The Journal of Biological Chemistry. 2010; 285: 24686–24694.
 Mitra A, Fillmore RA, Metge BJ, Rajesh M, Xi Y, King J, et al. Large isoform of MRJ (DNAJB6) reduces malignant activity of breast cancer. Breast Cancer Research. 2008; 10: R22.
 Wen KW, Damania B. Hsp90 and Hsp40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1. Oncogene. 2010; 29: 3532–3544.
 Di Michele M, Marcone S, Cicchillitti L, Della Corte A, Ferlini C, Scambia G, et al. Glycoproteomics of paclitaxel resistance in human epithelial ovarian cancer cell lines: towards the identification of putative biomarkers. Journal of Proteomics. 2010; 73: 879–898.
 Lyng H, Brøvig RS, Svendsrud DH, Holm R, Kaalhus O, Knutstad K, et al. Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer. BMC Genomics. 2006; 7: 268.
 Thomas CG, Spyrou G. ERdj5 sensitizes neuroblastoma cells to endoplasmic reticulum stress-induced apoptosis. Journal of Biological Chemistry. 2009; 284: 6282–6290.
 Shridhar V, Bible KC, Staub J, Avula R, Lee YK, Kalli K, et al. Loss of expression of a new member of the DNAJ protein family confers resistance to chemotherapeutic agents used in the treatment of ovarian cancer. Cancer Research. 2001; 61: 4258–4265.
 Solár P, Sytkowski AJ. Differentially expressed genes associated with cisplatin resistance in human ovarian adenocarcinoma cell line a2780. Cancer Letters. 2011; 309: 11–18.
 Lindsey JC, Lusher ME, Strathdee G, Brown R, Gilbertson RJ, Bailey S, et al. Epigenetic inactivation ofMCJ (DNAJD1) in malignant paediatric brain tumours. International Journal of Cancer. 2006; 118: 346–352.
 Qiu XB, Shao YM, Miao S, Wang L. The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cellular and Molecular Life Sciences. 2006; 63: 2560–2570.
 Piura B, Rabinovich A, Yavelsky V, Wolfson M. Heat shock proteins and malignancies of the female genital tract. Harefuah. 2002; 141: 969–972, 1010, 1009. (In Hebrew)
 Abd el All H, Rey A, Duvillard P. Expression of heat shock protein 70 and c- myc in cervical carcinoma. Anticancer Research. 1998; 18: 1533–1536.
 Cappello F, Bellafiore M, David S, Anzalone R, Zummo G. Ten kilodalton heat shock protein (HSP10) is overexpressed during carcinogenesis of large bowel and uterine exocervix. Cancer Letters. 2003; 196: 35–41.
 Cappello F, Bellafiore M, Palma A, David S, Marcianò V, Bartolotta T, et al. 60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. European Journal of Histochemistry. 2003; 47: 105–110.
 Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin JD, et al. A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 2008; 133: 978–993.
 Telang U, Morris ME. Effect of orally administered phenethyl isothio-cyanate on hepatic gene expression in rats. Molecular Nutrition & Food Research. 2010; 54: 1802–1806.
 Jiang S, Tang L, Zhao N, Yang W, Qiu Y, Chen HZ. A systems view of the differences between APOE epsilon4 carriers and non-carriers in Alzheimer’s disease. Frontiers in Aging Neuroscience. 2016; 8: 171.
 Piras IS, Krate J, Schrauwen I, Corneveaux JJ, Serrano GE, Sue L, et al. Whole transcriptome profiling of the human hippocampus suggests an involvement of the KIBRA rs17070145 polymorphism in differential activation of the MAPK signaling pathway. Hippocampus. 2017; 27: 784–793.
 Schulze HA, Häsler R, Mah N, Lu T, Nikolaus S, Costello CM, et al. From model cell line to in vivo gene expression: disease-related intestinal gene expression in IBD. Genes & Immunity. 2008; 9: 240–248.
 Sterrenberg JN, Blatch GL, Edkins AL. Human DNAJ in cancer and stem cells. Cancer Letters. 2011; 312: 129–142.
 Knox C, Luke GA, Blatch GL, Pesce E. Heat shock protein 40 (Hsp40) plays a key role in the virus life cycle. Virus Research. 2011; 160: 15–24.
 Lampis A, Carotenuto P, Vlachogiannis G, Cascione L, Hedayat S, Burke R, et al. MIR21 drives resistance to heat shock protein 90 inhibition in cholangiocarcinoma. Gastroenterology. 2018; 154: 1066–1079.e5.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.