Volume 24, Issue 5 (9-2020)                   ibj 2020, 24(5): 328-334 | Back to browse issues page

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Mashayekhi P, Noruzinia M, Khodaverdi S. Deregulation of Stemness-Related Genes in Endometriotic Mesenchymal Stem Cells: Further Evidence for Self-Renewal/Differentiation Imbalance. ibj. 2020; 24 (5) :328-334
URL: http://ibj.pasteur.ac.ir/article-1-3098-en.html
Background: Any irregularities in self-renewal/differentiation balance in endometriotic mesenchymal stem cells (MSCs) can change their fate and function, resulting in endometriosis development. This study aimed to evaluate the expression of OCT4 transcripts (OCT4A, OCT4B, and OCT4B1), SOX2, and NANOG in endometriotic MSCs to show their aberrant expression and to support self-renewal/differentiation imbalance in these cells. Methods: MSCs were isolated from three endometriotic and three normal endometrium samples and characterized and analyzed for the expressions of OCT4A, OCT4B, OCT4B1, SOX2, and NANOG using the quantitative real-time PCR. Results: The expressions of OCT4 transcripts and NANOG increased significantly in endometriotic MSCs, whereas SOX2 expression did not show any significant difference. Conclusion: Our findings provide further evidence for confirming the self-renewal/ differentiation imbalance in endometriotic MSCs, as the main underlying cause of endometriosis development. This study also paves the way for further research on endometriosis treatment by focusing on endometriotic stem cells.

1. Woodward PJ, Sohaey R, Mezzetti TP, Jr. Endometriosis: radiologic-pathologic correlation. Radiographics 2001; 21(1): 193-216. [DOI:10.1148/radiographics.21.1.g01ja14193]
2. Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. Journal of assisted reproduction 2010; 27(8): 441-447. [DOI:10.1007/s10815-010-9436-1]
3. Figueira PGM, Abrão MS, Krikun G, Taylor H. Stem cells in endometrium and their role in the pathogenesis of endometriosis. Annals of the New York academy of sciences 2011; 1221(1): 10-17. [DOI:10.1111/j.1749-6632.2011.05969.x]
4. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Human reproduction update 2011; 17(3): 327-346. [DOI:10.1093/humupd/dmq050]
5. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstetrics and gynecology 1984; 64(2): 151-154.
6. Domen J, Weissman IL. Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate. Molecular medicine today 1999; 5(5): 201-208. [DOI:10.1016/S1357-4310(99)01464-1]
7. Park JS, Lee JH, Kim M, Chang HJ, Hwang KJ, Chang KH. Endometrium from women with endometriosis shows increased proliferation activity. Fertility and sterility 2009; 92(4): 1246-1249. [DOI:10.1016/j.fertnstert.2009.04.025]
8. Klemmt PA, Carver JG, Kennedy SH, Koninckx PR, Mardon HJ. Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity. Fertility and sterility 2006; 85(3): 564-572. [DOI:10.1016/j.fertnstert.2005.08.046]
9. Olynik B, Rastegar M. The genetic and epigenetic journey of embryonic stem cells into mature neural cells. Frontiers in genetics 2012; 3: 81. [DOI:10.3389/fgene.2012.00081]
10. Mashayekhi P, Noruzinia M, Zeinali S, Khodaverdi S. Endometriotic mesenchymal stem cells epigenetic pathogenesis: deregulation of miR-200b, miR-145, and let7b in a functional imbalanced epigenetic disease. Cell journal (Yakhteh) 2019; 21(2): 179-185.
11. Bashti O, Noruzinia M, Garshasbi M, Abtahi M. miR-31 and miR-145 as potential non-invasive regulatory biomarkers in patients with endometriosis. Cell journal (Yakhteh) 2018; 20(1): 84-89.
12. Yoon DS, Kim YH, Jung HS, Paik S, Lee JW. Importance of Sox2 in maintenance of cell proliferation and multipotency of mesenchymal stem cells in low‐density culture. Cell proliferation 2011; 44(5): 428-440. [DOI:10.1111/j.1365-2184.2011.00770.x]
13. Huang CE, Hu FW, Yu CH, Tsai LL, Lee TH, Chou MY, Yu CC. Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells. International journal of molecular sciences 2014; 15(10): 18623-18639. [DOI:10.3390/ijms151018623]
14. Kashyap V, Rezende NC, Scotland KB, Shaffer SM, Persson JL, Gudas LJ, Mongan NP. Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem cells and development 2009; 18(7): 1093-1108. [DOI:10.1089/scd.2009.0113]
15. Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW. OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem cells 2008; 26(12): 3068-3074. [DOI:10.1634/stemcells.2008-0530]
16. Takeda J, Seino S, Bell GI. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic acids research 1992; 20(17): 4613-4620. [DOI:10.1093/nar/20.17.4613]
17. Niwa H, Miyazaki JI, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nature genetics2000; 24(4): 372-376. [DOI:10.1038/74199]
18. Ferro F, Spelat R, D'Aurizio F, Puppato E, Pandolfi M, Beltrami AP, Cesselli D, Falini G, Beltrami CA, Curcio F. Dental pulp stem cells differentiation reveals new insights in Oct4A dynamics. PLoS one 2012; 7(7): e41774. [DOI:10.1371/journal.pone.0041774]
19. Li D, Yang ZK, Bu JY, Xu CY, Sun H, Tang JB, Lin P, Cheng W, Huang N, Cui RJ. OCT4B modulates OCT4A expression as ceRNA in tumor cells. Oncology reports 2015; 33(5): 2622-2630. [DOI:10.3892/or.2015.3862]
20. Li SW, Wu XL, Dong CL, Xie XY, Wu JF, Zhang X. The differential expression of OCT4 isoforms in cervical carcinoma. PLoS one 2015; 10(3): e0118033. [DOI:10.1371/journal.pone.0118033]
21. Cortes-Dericks L, Yazd EF, Mowla SJ, Schmid RA, Karoubi G. Suppression of OCT4B enhances sensitivity of lung adenocarcinoma A549 cells to cisplatin via increased apoptosis. Anticancer research 2013; 33(12): 5365-5373.
22. Fujita J, Crane AM, Souza MK, Dejosez M, Kyba M, Flavell RA, Thomson JA, Zwaka TP. Caspase activity mediates the differentiation of embryonic stem cells. Cell stem cell 2008; 2(6): 595-601. [DOI:10.1016/j.stem.2008.04.001]
23. Papamichos SI, Kotoula V, Tarlatzis BC, Agorastos T, Papazisis K, Lambropoulos AF. OCT4B1 isoform: the novel OCT4 alternative spliced variant as a putative marker of stemness. Molecular human reproduction Oxford academic 2009; 15(5): 269-270. [DOI:10.1093/molehr/gap018]
24. Hejri SJA, Mirzaei MR, Arababadi MK, Hassanshahi G, Mahmoodi M. OCT4B1 Down-regulates self-renewal genes in cancer cell lines. Pharmaceutical sciences 2014; 19(4): 117-123.
25. Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y, Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. International journal of cancer 2011; 128(11): 2645-2652. [DOI:10.1002/ijc.25643]
26. Bell RA, Megeney LA. Evolution of caspase-mediated cell death and differentiation: twins separated at birth. Cell death and differentiation 2017; 24(8): 1359-1368. [DOI:10.1038/cdd.2017.37]
27. You L, Guo X, Huang Y. Correlation of cancer stem-cell markers OCT4, SOX2, and NANOG with clinicopathological features and prognosis in operative patients with rectal cancer. Yonsei medical journal 2018; 59(1): 35-42. [DOI:10.3349/ymj.2018.59.1.35]
28. Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal trans-differentiation. Cancer research 2010; 70(24): 10433-10444. [DOI:10.1158/0008-5472.CAN-10-2638]
29. Hwang JH, Oh JJ, Wang T, Jin YC, Lee JS, Choi JR, Lee KS, Joo JK, Lee HG. Identification of biomarkers for endometriosis in eutopic endometrial cells from patients with endometriosis using a proteomics approach. Molecular medicine reports 2013; 8(1): 183-188. [DOI:10.3892/mmr.2013.1469]
30. Chang JH, Au HK, Lee WC, Chi CC, Ling TY, Wang LM, Kao SH, Huang YH, Tzeng CR. Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis. Fertility and sterility 2013; 99(5): 1332-1339. [DOI:10.1016/j.fertnstert.2012.11.033]
31. da Silva PBG, dos Santos MCT, Rodini CO, Kaid C, Pereira MCL, Furukawa G, da Cruz DSG, Goldfeder MB, Rocha CRR, Rosenberg C, Okamoto O. High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells. Oncotarget 2017; 8(12): 19192-19204. [DOI:10.18632/oncotarget.15163]
32. Lin SC, Chung CH, Chung CH, Kuo MH, Hsieh CH, Chiu YF, Shieh YS, Chou YT, Wu CW. OCT4B mediates hypoxia-induced cancer dissemination. Oncogene 2019; 38: 1093-1105. [DOI:10.1038/s41388-018-0487-6]
33. Wen KM, Zhang GH, Li J, Chen ZQ, Cheng YL, Su X, Zeng QL. OCT4B1 promotes cell growth, migration and invasion suppressing sensitivity to οxaliplatin in colon cancer. Oncology report 2015; 34(6): 2943-2952. [DOI:10.3892/or.2015.4286]
34. Yu AQ, Ding Y, Li CL, Yang Y, Yan SR, Li DS. TALEN-induced disruption of Nanog expression results in reduced proliferation, invasiveness and migration, increased chemosensitivity and reversal of EMT in HepG2 cells. Oncology report 2016; 35(3): 1657-1663 [DOI:10.3892/or.2015.4483]
35. Jaenisch R, Young R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 2008; 132(4): 567-582. [DOI:10.1016/j.cell.2008.01.015]
36. Pietersen AM, van Lohuizen M. Stem cell regulation by polycomb repressors: postponing commitment. Current opinion in cell biology 2008; 20(2): 201-207. [DOI:10.1016/j.ceb.2008.01.004]
37. Aghajanova L, Hamilton A, Kwintkiewicz J, Vo K, Giudice L. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biology of reproduction 2009; 80(1): 105-114. [DOI:10.1095/biolreprod.108.070300]

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