Investigation Association between Line-1 And MORC2 Expression in Different Types of Cancers
DOI:
https://doi.org/10.51699/cajmns.v4i6.2202Keywords:
line-1, MORC2, Cancer, gene expressionAbstract
Line-1 elements act as an engine in alteration human genomic DNA. These elements continue to insert new insertions facilitating genomic diversity and sometimes causing disease including cancer. Mobilization of line-1 could act as mutagenesis and exon skipping. However, there are different mechanisms can regulate mRNA transcript of line-1 elements.. MORC2 gene was suggested to be a novel participant in regulation line-1 transcription, acting by binding HUSH complex and suppress active line-1 element. Thus, in current project we are interested to evaluate the level expression of line-1 and MORC2 in some cases of cancer compared with healthy group as well as evaluating the correlation between line-1 and MORC2 expression to investigate how regulatory factors affect line-1 expression in several cases of cancer. This study was first assay conducted in Iraq. However, this study started with collecting whole blood samples of patients and healthy group. Then, RNA was extracted and created cDNA to set up RT-qPCR, which used to analyze mRNA level of both genes line-1 and MORC2. Most cases of cancer expressed line-1 including testicular, breast, colon, pharyngeal, stomach, prostate, rectal, pancreatic, brain, lung, and bone respectively at different levels of p-value. Brain cancer was highly expressed line-1. MORC2 gene was expressed in rectal, pancreatic, brain, lymphoma, testicular, cervical, ovarian, pharyngeal, bone, lung, and leukemia at p-value 0.05. Line-1 is substantially more elevated than MORC2 in several cancer types, and Line-1 expression has a significantly negative correlation with MORC2 expression in cancer patients.
References
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36. Zhang X, Zhang R and Yu J (2020) New understanding of the relevant role of LINE-1 retrotransposition in human disease and immune modulation. Frontiers in cell and developmental biology 8:657.
2. Beck CR, Garcia-Perez JL, Badge RM and Moran JV (2011) LINE-1 elements in structural variation and disease. Annual review of genomics and human genetics 12:187-215.
3. Belancio VP, Blask DE, Deininger P, Hill SM and Jazwinski SM (2015) The aging clock and circadian control of metabolism and genome stability. Frontiers in genetics 5:455.
4. Burns KH (2022) Repetitive DNA in disease. Science 376:353-354.
5. Das A, Vijayan M, Walton EM, Stafford VG, Fiflis DN and Asokan A (2022) Epigenetic silencing of recombinant adeno-associated virus genomes by NP220 and the HUSH complex. Journal of Virology 96:e02039-02021.
6. Ding Q-s, Zhang L, Wang B-c, Zeng Z, Zou X-q, Cao P-b, Zhou G-m, Tang M, Wu L and Wu L-l (2018) Aberrant high expression level of MORC2 is a common character in multiple cancers. Human Pathology 76:58-67.
7. Garland W, Müller I, Wu M, Schmid M, Imamura K, Rib L, Sandelin A, Helin K and Jensen TH (2022) Chromatin modifier HUSH co-operates with RNA decay factor NEXT to restrict transposable element expression. Molecular Cell 82:1691-1707. e1698.
8. Gasior SL, Wakeman TP, Xu B and Deininger PL (2006) The human LINE-1 retrotransposon creates DNA double-strand breaks. Journal of molecular biology 357:1383-1393.
9. Goodier JL and Kazazian HH (2008) Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135:23-35.
10. Guddeti RK, Chutani N and Pakala SB (2021) MORC2 Interactome: Its Involvement in Metabolism and Cancer. Biophysical Reviews 13:507-514.
11. Hancks DC and Kazazian Jr HH (2012) Active human retrotransposons: variation and disease. Current opinion in genetics & development 22:191-203.
12. Iskow RC, McCabe MT, Mills RE, Torene S, Pittard WS, Neuwald AF, Van Meir EG, Vertino PM and Devine SE (2010) Natural mutagenesis of human genomes by endogenous retrotransposons. Cell 141:1253-1261.
13. Jönsson ME, Garza R, Johansson PA and Jakobsson J (2020) Transposable elements: a common feature of neurodevelopmental and neurodegenerative disorders. Trends in Genetics 36:610-623.
14. Kazazian HH and Moran JV (2017) Mobile DNA in Health and Disease. New England Journal of Medicine 377:361-370.
15. Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C and Antonacci F (2008) Mapping and sequencing of structural variation from eight human genomes. Nature 453:56-64.
16. Kikuno R, Nagase T, Ishikawa K-i, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N and Ohara O (1999) Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA research 6:197-205.
17. Li D-Q, Nair SS and Kumar R (2013) The MORC family: new epigenetic regulators of transcription and DNA damage response. Epigenetics 8:685-693.
18. Liu N, Lee CH, Swigut T, Grow E, Gu B, Bassik MC and Wysocka J (2018) Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators. Nature 553:228-232.
19. Miki Y, Nishisho I, Horii A, Miyoshi Y, Utsunomiya J, Kinzler KW, Vogelstein B and Nakamura Y (1992) Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer research 52:643-645.
20. Moissiard G, Cokus SJ, Cary J, Feng S, Billi AC, Stroud H, Husmann D, Zhan Y, Lajoie BR and McCord RP (2012) MORC family ATPases required for heterochromatin condensation and gene silencing. Science 336:1448-1451.
21. Moran JV, DeBerardinis RJ and Kazazian Jr HH (1999) Exon shuffling by L1 retrotransposition. Science 283:1530-1534.
22. Morse B, Rotherg PG, South VJ, Spandorfer JM and Astrin SM (1988) Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma. Nature 333:87-90.
23. Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze AV, Mikheenko A, Vollger MR, Altemose N, Uralsky L and Gershman A (2022) The complete sequence of a human genome. Science 376:44-53.
24. Pandiloski N, Horvath V, Karlsson OE, Christoforidou G, Dorazehi F, Koutounidou S, Matas J, Gerdes P, Garza R and Jönsson ME (2023) DNA methylation governs the sensitivity of repeats to restriction by the HUSH-MORC2 corepressor. bioRxiv:2023.2006. 2021.545516.
25. Robbez-Masson L, Tie CH, Conde L, Tunbak H, Husovsky C, Tchasovnikarova IA, Timms RT, Herrero J, Lehner PJ and Rowe HM (2018) The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes. Genome research 28:836-845.
26. Rodić N, Sharma R, Sharma R, Zampella J, Dai L, Taylor MS, Hruban RH, Iacobuzio-Donahue CA, Maitra A and Torbenson MS (2014) Long interspersed element-1 protein expression is a hallmark of many human cancers. The American journal of pathology 184:1280-1286.
27. Scott EC and Devine SE (2017) The role of somatic L1 retrotransposition in human cancers. Viruses 9:131.
28. Seczynska M, Bloor S, Cuesta SM and Lehner PJ (2022) Genome surveillance by HUSH-mediated silencing of intronless mobile elements. Nature 601:440-445.
29. Seczynska M and Lehner PJ (2023) The sound of silence: mechanisms and implications of HUSH complex function. Trends in Genetics.
30. Seleme MdC, Vetter MR, Cordaux R, Bastone L, Batzer MA and Kazazian Jr HH (2006) Extensive individual variation in L1 retrotransposition capability contributes to human genetic diversity. Proceedings of the National Academy of Sciences 103:6611-6616.
31. Soifer HS (2006) Do small RNAs interfere with LINE-1? Journal of Biomedicine and Biotechnology 2006.
32. Tunbak H, Enriquez-Gasca R, Tie CH, Gould PA, Mlcochova P, Gupta RK, Fernandes L, Holt J, van der Veen AG and Giampazolias E (2020) The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s. Nature communications 11:5387.
33. Wang GL, Wang CY, Cai XZ, Chen W, Wang XH and Li F (2010) Identification and expression analysis of a novel CW‐type zinc finger protein MORC2 in cancer cells. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 293:1002-1009.
34. Wissing S, Montano M, Garcia-Perez JL, Moran JV and Greene WC (2011) Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells. Journal of biological chemistry 286:36427-36437.
35. Zhang S, Guo A, Wang H, Liu J, Dong C, Ren J and Wang G (2023) Oncogenic MORC2 in cancer development and beyond. Genes & diseases.
36. Zhang X, Zhang R and Yu J (2020) New understanding of the relevant role of LINE-1 retrotransposition in human disease and immune modulation. Frontiers in cell and developmental biology 8:657.
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Published
2023-12-21
How to Cite
AL-Abdullah, W. A. W. . (2023). Investigation Association between Line-1 And MORC2 Expression in Different Types of Cancers. Central Asian Journal of Medical and Natural Science, 4(6), 1143–1151. https://doi.org/10.51699/cajmns.v4i6.2202
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