L1Hs and MPP8 Genes Expression Correlation with Several Types of Carcinoma Tumors

Main Article Content

Wisam Abdan Wawi AL Abdullah

Abstract

L1Hs is a major player in genome evolution and genetic variability. Aberrant activity of L1Hs element is common in several human cancers. It's specific function is poorly characterized  epigenetic regulation via human silencing Hub (HUSH) complex is critical to inhibit L1Hs activity. MPP8 is a subunit of HUSH complex and recently it has been suggested to inhibit L1Hs elements transcription. Thus, this assay was aimed to assess the expression level of L1Hs and MPP8 genes in cancer whole blood samples and healthy group utilizing qPCR assay. Generally, L1Hs gene significantly up regulated two times in patients' blood samples compared with healthy group. MPP8 gene up regulated approximately two times in cancer samples compared with healthy group. Testes, prostate, colon and cervical cancers were significantly expressed L1Hs more than MPP8 expression. While there is no significant differ in expression level of MPP8 and L1Hs genes in breast, bladder and ovary cancers.

Article Details

How to Cite
Wisam Abdan Wawi AL Abdullah. (2023). L1Hs and MPP8 Genes Expression Correlation with Several Types of Carcinoma Tumors. International Journal of Medical Science and Clinical Research Studies, 3(10), 2445–2450. https://doi.org/10.47191/ijmscrs/v3-i10-61
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References

I. 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.

II. Burns KH (2017) Transposable elements in cancer. Nature Reviews Cancer 17:415-424.

III. Chang Y, Horton JR, Bedford MT, Zhang X and Cheng X (2011) Structural insights for MPP8 chromodomain interaction with histone H3 lysine 9: potential effect of phosphorylation on methyl-lysine binding. Journal of molecular biology 408:807-814.

IV. Chen J, Rattner A and Nathans J (2006) Effects of L1 retrotransposon insertion on transcript processing, localization and accumulation: lessons from the retinal degeneration 7 mouse and implications for the genomic ecology of L1 elements. Human molecular genetics 15:2146-2156.

V. Chen L, Dahlstrom JE, Lee S-H and Rangasamy D (2012) Naturally occurring endo-siRNA silences LINE-1 retrotransposons in human cells through DNA methylation. Epigenetics 7:758-771.

VI. Cuellar TL, Herzner A-M, Zhang X, Goyal Y, Watanabe C, Friedman BA, Janakiraman V, Durinck S, Stinson J and Arnott D (2017) Silencing of retrotransposons by SETDB1 inhibits the interferon response in acute myeloid leukemia. Journal of Cell Biology 216:3535-3549.

VII. Deniz Ö, Frost JM and Branco MR (2019) Regulation of transposable elements by DNA modifications. Nature Reviews Genetics 20:417-431.

VIII. Ewing AD, Gacita A, Wood LD, Ma F, Xing D, Kim M-S, Manda SS, Abril G, Pereira G and Makohon-Moore A (2015) Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution. Genome research 25:1536-1545.

IX. Gu Z, Liu Y, Zhang Y, Cao H, Lyu J, Wang X, Wylie A, Newkirk SJ, Jones AE and Lee Jr M (2021) Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia. Nature genetics 53:672-682.

X. Hancks DC and Kazazian HH (2016) Roles for retrotransposon insertions in human disease. Mobile DNA 7:1-28.

XI. Healton SE, Pinto HD, Mishra LN, Hamilton GA, Wheat JC, Swist-Rosowska K, Shukeir N, Dou Y, Steidl U and Jenuwein T (2020) H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction. Proceedings of the National Academy of Sciences 117:14251-14258.

XII. Huang CRL, Burns KH and Boeke JD (2012) Active transposition in genomes. Annual review of genetics 46:651-675.

XIII. Ishak CA, Marshall AE, Passos DT, White CR, Kim SJ, Cecchini MJ, Ferwati S, MacDonald WA, Howlett CJ and Welch ID (2016) An RB-EZH2 complex mediates silencing of repetitive DNA sequences. Molecular cell 64:1074-1087.

XIV. Jönsson ME, Ludvik Brattås P, Gustafsson C, Petri R, Yudovich D, Pircs K, Verschuere S, Madsen S, Hansson J and Larsson J (2019) Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors. Nature communications 10:1-11.

XV. Kato M, Takemoto K and Shinkai Y (2018) A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing. Nature communications 9:1683.

XVI. Kazazian Jr HH and Moran JV (2017) Mobile DNA in health and disease. New England Journal of Medicine 377:361-370.

XVII. Lander E, Linton L, Birren B, Nusbaum C, Zody M, Baldwin J, Devon K, Dewar K, Doyle M and FitzHugh W many others. 2001. Initial sequencing and analysis of the human genome. Nature 409:860-921.

XVIII. Liang X, Liu T, Zhang W, Zhang K, Guo S and Liang J (2017) Lentivirus‐mediated knockdown of M‐phase phosphoprotein 8 inhibits proliferation of colon cancer cells. Biotechnology and Applied Biochemistry 64:911-917.

XIX. 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.

XX. Livak KJ and Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods 25:402-408.

XXI. Matsumoto-Taniura N, Pirollet F, Monroe R, Gerace L and Westendorf J (1996) Identification of novel M phase phosphoproteins by expression cloning. Molecular biology of the cell 7:1455-1469.

XXII. Müller I, Moroni AS, Shlyueva D, Sahadevan S, Schoof EM, Radzisheuskaya A, Højfeldt JW, Tatar T, Koche RP and Huang C (2021) MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells. Nature Communications 12:3034.

XXIII. Nishigaki M, Kawada Y, Misaki T, Murata K, Goshima T, Hirokawa T, Yamada C, Shimada M and Nakanishi M (2013) Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates chromatin dissociation. Biochemical and biophysical research communications 432:654-659.

XXIV. Pappalardo X and Barra V (2021) Losing DNA methylation at repetitive elements and breaking bad. Epigenetics Chromatin 14 (1): 25.

XXV. Payer LM and Burns KH (2019) Transposable elements in human genetic disease. Nature Reviews Genetics 20:760-772.

XXVI. Puszyk W, Down T, Grimwade D, Chomienne C, Oakey RJ, Solomon E and Guidez F (2013) The epigenetic regulator PLZF represses L1 retrotransposition in germ and progenitor cells. The EMBO journal 32:1941-1952.

XXVII. Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F, Demeulemeester J, Santamarina M, Ju YS, Temes J and Garcia-Souto D (2020) Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nature genetics 52:306-319.

XXVIII. Scott EC, Gardner EJ, Masood A, Chuang NT, Vertino PM and Devine SE (2016) A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer. Genome research 26:745-755.

XXIX. Sheng W, LaFleur MW, Nguyen TH, Chen S, Chakravarthy A, Conway JR, Li Y, Chen H, Yang H and Hsu P-H (2018) LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 174:549-563. e519.

XXX. Shukla R, Upton KR, Muñoz-Lopez M, Gerhardt DJ, Fisher ME, Nguyen T, Brennan PM, Baillie JK, Collino A and Ghisletti S (2013) Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell 153:101-111.

XXXI. Solyom S, Ewing AD, Rahrmann EP, Doucet T, Nelson HH, Burns MB, Harris RS, Sigmon DF, Casella A and Erlanger B (2012) Extensive somatic L1 retrotransposition in colorectal tumors. Genome research 22:2328-2338.

XXXII. Tchasovnikarova IA, Timms RT, Matheson NJ, Wals K, Antrobus R, Göttgens B, Dougan G, Dawson MA and Lehner PJ (2015) Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348:1481-1485.

XXXIII. Thomas CA, Tejwani L, Trujillo CA, Negraes PD, Herai RH, Mesci P, Macia A, Crow YJ and Muotri AR (2017) Modeling of TREX1-dependent autoimmune disease using human stem cells highlights L1 accumulation as a source of neuroinflammation. Cell stem cell 21:319-331. e318.

XXXIV. Tie CH, Fernandes L, Conde L, Robbez‐Masson L, Sumner RP, Peacock T, Rodriguez‐Plata MT, Mickute G, Gifford R and Towers GJ (2018) KAP 1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control. EMBO reports 19:e45000.

XXXV. Timms RT, Tchasovnikarova IA and Lehner PJ (2016) Position‐effect variegation revisited: HUSHing up heterochromatin in human cells. BioEssays 38:333-343.

XXXVI. 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.

XXXVII. Wang Y, Xiao H, Wang C, Wu H, He H, Yao C, Cui J and Li W (2020) M‐phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl‐2 and EMT‐related signaling pathways. Journal of Cellular Biochemistry 121:2330-2342.

XXXVIII. Yuan B, Lin L, Ying Z-Y, Ying M-X, Zhou Q-Y and Shi L (2017) Repression of M-phase phosphoprotein 8 inhibits melanoma growth and metastasis in vitro and in vivo. International Journal of Clinical and Experimental Pathology 10:12003.