Skip to main content

Advertisement

SpringerLink
Log in

Linc-ROR Promotes EMT by Targeting miR-204-5p/SMAD4 in Endometriosis

  • Endometriosis: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Endometriosis (EMs) is a systemic and chronic disease with cancer-like feature, namely, distant implantation, which caused heavy healthy burden of nearly 200 million females. LncRNAs have been proved as new modulators in epithelial–mesenchymal transition (EMT) and EMs. Quantitative real-time PCR was conducted to measure the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR), and miR-204-5p in ectopic endometrium (n = 25), eutopic endometrium (n = 20), and natural control endometrium (n = 22). Overexpression of Linc-ROR, knockdown or overexpression of miR-204-5p in End1/E6E7 and Ishikawa cells, was conducted to detect the function of Linc-ROR and miR-204-5p in EMs. Furthermore, luciferase reports were used to confirm the combination of Linc-ROR and miR-204-5p and the combination between miR-204-5p and SMAD4. Cell-Counting Kit-8, EdU assay, transwell assays, and Western blotting were used to detect the function of Linc-ROR and miR-204-5p in EMs cancer-like behaviors and EMT process. Linc-ROR was up-regulated in ectopic endometrium. Overexpressed Linc-ROR promotes cell proliferation, invasion, and EMT process. Linc-ROR regulated the EMT process, cellular proliferation, and invasion of EMs via binding to miR-204-5p. In addition, overexpression of Linc-ROR up-regulated SMAD4, a target protein of miR-204-5p, with which regulated EMT process and cancer-like behaviors in EMs together. Linc-ROR/miR-204-5p/SMAD4 axis plays a vital role in regulation EMT process in EMs, which might become a novel therapeutic targets and powerful biomarkers in EMs therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Not applicable.

Code Availability

Not applicable.

Abbreviations

EMs:

Endometriosis

EMT:

Epithelial–mesenchymal transition

ncRNA:

Non-coding RNA

ISK:

Ishikawa

E6E7:

End1/E6E7

E-cad:

E-cadherin

VIM:

Vimentin

ceRNA:

Competing endogenous RNA

LncRNA:

Long non-coding RNA

PBS:

Phosphate-buffered saline

CCK-8:

Cell counting kit-8

qRT-PCR:

Quantitative reverse-transcription polymerase chain reaction

IHC:

Immunohistochemistry

EC:

Ectopic endometrium

EU:

Eutopic endometrium

NC:

Endometrium from the control group

R-SMAD:

Receptor-regulated SMAD

References

  1. Eisenberg VH, Weil C, Chodick G, Shalev V. Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members. BJOG. 2018;125:55–62.

    Article  CAS  PubMed  Google Scholar 

  2. de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376:730–8.

    Article  PubMed  Google Scholar 

  3. Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M, Wei J. Endometriosis. Endocr Rev. 2019;40:1048–79.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. New Engl J Med. 2017;377:28–40.

    Article  CAS  PubMed  Google Scholar 

  5. Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019;15:666–82.

    Article  PubMed  Google Scholar 

  6. Guo SW. Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology. Hum Reprod Update. 2020;26:423–49.

    Article  PubMed  Google Scholar 

  7. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69–84.

  8. Bilyk O, Coatham M, Jewer M, Postovit LM. Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology. Front Oncol. 2017;7:145.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Saunders PTK, Horne AW. Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell. 2021;184:2807–24.

    Article  CAS  PubMed  Google Scholar 

  10. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014;505:344–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Thomson DW, Dinger ME. Endogenous microRNA sponges: evidence and controversy. Nat Rev Genet. 2016;17(5):272–83.

  12. Abba ML, Patil N, Leupold JH, Moniuszko M, Utikal J, Niklinski J, Allgayer H. MicroRNAs as novel targets and tools in cancer therapy. Cancer Lett. 2017;387:84–94.

    Article  CAS  PubMed  Google Scholar 

  13. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Vigano P. Endometriosis. Nat Rev Dis Primers. 2018;4:9.

    Article  PubMed  Google Scholar 

  14. Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, Martin DC. The pathogenesis of endometriosis: molecular and cell biology insights. Int J Mol Sci. 2019;20(22):5615.

  15. Wang X, Zhang J, Liu X, Wei B, Zhan L. Long noncoding RNAs in endometriosis: Biological functions, expressions, and mechanisms. J Cell Physiol. 2021;236:6–14.

    Article  CAS  PubMed  Google Scholar 

  16. Lin D, Huang Q, Wu R, Dai S, Huang Z, Ren L, Huang S, Chen Q. Long non-coding RNA AFAP1-AS1 promoting epithelial-mesenchymal transition of endometriosis is correlated with transcription factor ZEB1. Am J Reprod Immunol. 2019;81(1):e13074.

    Article  PubMed  Google Scholar 

  17. Mai H, Wei Y, Yin Y, Huang S, Lin H, Liao Y, Liu X, Chen X, Shi H, Liu C, Xu H. LINC01541 overexpression attenuates the 17 beta-Estradiol-induced migration and invasion capabilities of endometrial stromal cells. Syst Biol Reprod Med. 2019;65:214–22.

    Article  CAS  PubMed  Google Scholar 

  18. Liu H, He H, Zhang Z, Wang L, Zhang L, Liu Y, Xiong W. Upregulation of the long noncoding RNA UBOX5 antisense RNA 1 (UBOX5-AS1) under hypoxic conditions promotes epithelial-mesenchymal transition in endometriosis. Ann Transl Med. 2021;9(9):790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liang Z, Chen Y, Zhao Y, Xu C, Zhang A, Zhang Q, Wang D, He J, Hua W, Duan P. miR-200c suppresses endometriosis by targeting MALAT1 in vitro and in vivo. Stem Cell Res Ther. 2017;8:251.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Du Y, Zhang Z, Xiong W, Li N, Liu H, He H, Li Q, Liu Y, Zhang L. Estradiol promotes EMT in endometriosis via MALAT1/miR200s sponge function. Reproduction. 2019;157:179–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang S, Yi M, Zhang X, Zhang T, Jiang L, Cao L, Zhou Y, Fang X. Effects of CDKN2B-AS1 on cellular proliferation, invasion and AKT3 expression are attenuated by miR-424-5p in a model of ovarian endometriosis. Reprod Biomed Online. 2021;42:1057–66.

    Article  PubMed  Google Scholar 

  22. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839–52.

    Article  CAS  PubMed  Google Scholar 

  23. Wang S, Zhang M, Zhang T, Deng J, Xia X, Fang X. microRNA-141 inhibits TGF-β1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-β1/SMAD2 signalling pathway in endometriosis. Arch Gynecol Obstet. 2020;301:707–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–84.

    Article  CAS  PubMed  Google Scholar 

  25. Derynck R, Budi EH. Specificity, versatility, and control of TGF-beta family signaling. Sci Signal. 2019;12(570):eaav5183.

  26. Azar R, Alard A, Susini C, Bousquet C, Pyronnet S. 4E-BP1 is a target of Smad4 essential for TGFbeta-mediated inhibition of cell proliferation. EMBO J. 2009;28:3514–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang J, Guan W, Xu X, Wang F, Li X, Xu G. A novel homeostatic loop of sorcin drives paclitaxel-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human ovarian cancer. Oncogene. 2021;40:4906–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ping S, Ma C, Liu P, Yang L, Yang X, Wu Q, Zhao X, Gong B. Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data. Arch Gynecol Obstet. 2016;293:797–804.

    Article  CAS  PubMed  Google Scholar 

  29. Xu XY, Zhang J, Qi YH, Kong M, Liu SA, Hu JJ. Linc-ROR promotes endometrial cell proliferation by activating the PI3K-Akt pathway. Eur Rev Med Pharmacol Sci. 2018;22:2218–25.

    PubMed  Google Scholar 

  30. Inoue S, Hirota Y, Ueno T, Fukui Y, Yoshida E, Hayashi T, Kojima S, Takeyama R, Hashimoto T, Kiyono T, Ikemura M, Taguchi A, Tanaka T, Tanaka Y, Sakata S, Takeuchi K, Muraoka A, Osuka S, Saito T, Oda K, Osuga Y, Terao Y, Kawazu M, Mano H. Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations. Nat Commun. 2019;10:5785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gao H, Wang T, Zhang P, Shang M, Gao Z, Yang F, Liu R. Linc-ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR-204-5p/MDM2. J Cell Physiol. 2020;235:2325–35.

    Article  CAS  PubMed  Google Scholar 

  32. Zhi Y, Abudoureyimu M, Zhou H, Wang T, Feng B, Wang R, Chu X. FOXM1-Mediated LINC-ROR Regulates the Proliferation and Sensitivity to Sorafenib in Hepatocellular Carcinoma. Mol Ther Nucleic Acids. 2019;16:576–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhan HX, Wang Y, Li C, Xu JW, Zhou B, Zhu JK, Han HF, Wang L, Wang YS, Hu SY. LincRNA-ROR promotes invasion, metastasis and tumor growth in pancreatic cancer through activating ZEB1 pathway. Cancer Lett. 2016;374:261–71.

    Article  CAS  PubMed  Google Scholar 

  34. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–821.

  35. Xu J, Zhu X, Wu L, Yang R, Yang Z, Wang Q, Wu F. MicroRNA-122 suppresses cell proliferation and induces cell apoptosis in hepatocellular carcinoma by directly targeting Wnt/β-catenin pathway. Liver Int. 2012;32:752–60.

    Article  CAS  PubMed  Google Scholar 

  36. Sun Y, Li Q, Gui H, Xu DP, Yang YL, Su DF, Liu X. MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines. Cell Res. 2013;23:1270–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Matsuzaki S, Pouly JL, Canis M. In vitro and in vivo effects of MK2206 and chloroquine combination therapy on endometriosis: autophagy may be required for regrowth of endometriosis. Br J Pharmacol. 2018;175:1637–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bayoglu Tekin Y, Guven S, Kirbas A, Kalkan Y, Tumkaya L, Guvendag Guven ES. Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis? Eur J Obstet Gynecol Reprod Biol. 2015;184:1–6.

    Article  CAS  PubMed  Google Scholar 

  39. Chen J, Zhong Y, Li L. miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC). J Transl Med. 2020;18:69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang JR, Liu B, Zhou L, Huang YX. MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer. Cancer Biomark. 2019;24:159–72.

    Article  CAS  PubMed  Google Scholar 

  41. Luo L, Chi H, Ling J. MiR-124–3p suppresses glioma aggressiveness via targeting of Fra-2. Pathol Res Pract. 2018;214:1825–1834.

  42. Zeng T, Luo L, Huang Y, Ye X, Lin J. Upregulation of miR-138 Increases Sensitivity to Cisplatin in Hepatocellular Carcinoma by Regulating EZH2. Biomed Res Int. 2021;2021:6665918.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zhu D, Gu L, Li Z, Jin W, Lu Q, Ren T. MiR-138–5p suppresses lung adenocarcinoma cell epithelial-mesenchymal transition, proliferation and metastasis by targeting ZEB2. Pathol Res Pract. 2019;215:861–872.

  44. Zhang F, Li T, Han L, Qin P, Wu Z, Xu B, Gao Q, Song Y. TGFβ1-induced down-regulation of microRNA-138 contributes to epithelial-mesenchymal transition in primary lung cancer cells. Biochem Biophys Res Commun. 2018;496:1169–75.

    Article  CAS  PubMed  Google Scholar 

  45. Li D, He C, Wang J, Wang Y, Bu J, Kong X, Sun D. MicroRNA-138 Inhibits Cell Growth, Invasion, and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop. Oncol Res. 2018;26:385–400.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Si H, Chen P, Li H, Wang X. Long non-coding RNA H19 regulates cell growth and metastasis via miR-138 in breast cancer. Am J Transl Res. 2019;11:3213–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhao C, Ling X, Li X, Hou X, Zhao D. MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1. Breast Cancer. 2019;26:817–25.

    Article  PubMed  Google Scholar 

  48. Tang N, Dong Y, Liu J, Zhao H. Silencing of Long Non-coding RNA NEAT1 Upregulates miR-195a to Attenuate Intervertebral Disk Degeneration via the BAX/BAK Pathway. Front Mol Biosci. 2020;7:147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bai J, Xu J, Zhao J, Zhang R. lncRNA SNHG1 cooperated with miR-497/miR-195-5p to modify epithelial-mesenchymal transition underlying colorectal cancer exacerbation. J Cell Physiol. 2020;235:1453–68.

    Article  CAS  PubMed  Google Scholar 

  50. Zhao X, Dai L, Yue Q, Wang H, Wang XU, Li Y, Chen R. MiR-195 inhibits migration, invasion and epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells by targeting SOX4. J Biosci (Bangalore). 2019:44(6):146.

  51. Liang M, Huang G, Liu Z, Wang Q, Yu Z, Liu Z, Lin H, Li M, Zhou X, Zheng Y. Elevated levels of hsa_circ_006100 in gastric cancer promote cell growth and metastasis via miR-195/GPRC5A signalling. Cell Prolif. 2019;52: e12661.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Zhao L, Tian C, Xiao E, Du J, Liang J, Chen X, Chi W. Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO. Open Med (Wars). 2020;15:728–38.

    Article  CAS  PubMed  Google Scholar 

  53. Wang H, Qian J, Xia X, Ye B. Long non-coding RNA OIP5-AS1 serves as an oncogene in laryngeal squamous cell carcinoma by regulating miR-204-5p/ZEB1 axis. Naunyn-Schmiedeberg’s Arch Pharmacol. 2020;393:2177–84.

    Article  CAS  Google Scholar 

  54. Sui H, Fan S, Liu W, Li Y, Zhang X, Du Y, Bao H. LINC00028 regulates the development of TGFbeta1-treated human tenon capsule fibroblasts by targeting miR-204–5p. Biochem Biophys Res Commun. 2020;525(1):197–203.

    Article  CAS  Google Scholar 

  55. Liang C, Yang Y, Guan J, Lv T, Qu S, Fu Q, Zhao H. LncRNA UCA1 sponges miR-204–5p to promote migration, invasion and epithelial-mesenchymal transition of glioma cells via upregulation of ZEB1. Pathol Res Pract. 2018;214:1474–1481.

  56. Huang J, Wang X, Wen G, Ren Y. miRNA-205-5p functions as a tumor suppressor by negatively regulating VEGFA and PI3K/Akt/mTOR signaling in renal carcinoma cells. Oncol Rep 2019;42(5):1677–88.

  57. Lu J, Lin Y, Li F, Ye H, Zhou R, Jin Y, Li B, Xiong X, Cheng N. MiR-205 suppresses tumor growth, invasion, and epithelial-mesenchymal transition by targeting SEMA4C in hepatocellular carcinoma. FASEB J. 2018;32(11):6123–34.

    Article  CAS  Google Scholar 

  58. Dai B, Zhou G, Hu Z, Zhu G, Mao B, Su H, Jia Q. MiR-205 suppresses epithelial-mesenchymal transition and inhibits tumor growth of human glioma through down-regulation of HOXD9. Biosci Rep. 2019;39(5):BSR20181989.

  59. Vosgha H, Ariana A, Smith RA, Lam AK. miR-205 targets angiogenesis and EMT concurrently in anaplastic thyroid carcinoma. Endocr Relat Cancer. 2018;25:323–37.

    Article  CAS  PubMed  Google Scholar 

  60. Chen W, Kong KK, Xu XK, Chen C, Li H, Wang FY, Peng XF, Zhang Z, Li P, Li JL, Li FC. Downregulation of miR205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway. Int J Oncol. 2018;52:485–95.

    CAS  PubMed  Google Scholar 

  61. Gulei D, Magdo L, Jurj A, Raduly L, Cojocneanu-Petric R, Moldovan A, Moldovan C, Florea A, Pasca S, Pop LA, Moisoiu V, Budisan L, Pop-Bica C, Ciocan C, Buiga R, Muresan MS, Stiufiuc R, Ionescu C, Berindan-Neagoe I. The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal transition in colon cancer cells by indirectly up-regulating E-cadherin expression. Cell Death Dis. 2018;9:66.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Standart N, Jackson RJ. MicroRNAs repress translation of m7G ppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. Genes Dev. 2007;21:1975–82.

    Article  CAS  PubMed  Google Scholar 

  63. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007;318:1931–4.

    Article  CAS  PubMed  Google Scholar 

  64. Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, Liu S, Schwind S, Santhanam R, Hickey CJ, Becker H, Chandler JC, Andino R, Cortes J, Hokland P, Huettner CS, Bhatia R, Roy DC, Liebhaber SA, Caligiuri MA, Marcucci G, Garzon R, Croce CM, Calin GA, Perrotti D. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140:652–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Weis-Banke SE, Lerdrup M, Kleine-Kohlbrecher D, Mohammad F, Sidoli S, Jensen ON, Yanase T, Nakamura T, Iwase A, Stylianou A, Abu-Rustum NR, Aghajanian C, Soslow R, Da Cruz Paula A, Koche RP, Weigelt B, Christensen J, Helin K, Cloos PAC. Mutant FOXL2(C134W) Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors. Cancer Res. 2020;80:3466–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Peng C, Wang Y, Ji L, Kuang L, Yu Z, Li H, Zhang J, Zhao J. LncRNA-MALAT1/miRNA-204–5p/Smad4 axis regulates epithelial-mesenchymal transition, proliferation and migration of lens epithelial cells. Curr Eye Res. 2021;46(8):1137–47.

    Article  CAS  PubMed  Google Scholar 

  67. Qu J, Zhu Y, Wu X, Zheng J, Hou Z, Cui Y, Mao Y, Liu J. Smad3/4 Binding to Promoter II of P450arom So As to Regulate Aromatase Expression in Endometriosis. Reprod Sci. 2017;24:1187–94.

    Article  CAS  PubMed  Google Scholar 

  68. Zheng J, Qu J, Lu P, Hou Z, Cui Y, Mao Y, Qi X, Ji H, Liu J. Activin A Stimulates Aromatase via the ALK4-Smad Pathway in Endometriosis. Biomed Res Int. 2016;2016:5791510.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank AiMi Academic Services (www.aimieditor.com) for the English language editing and review services.

Funding

This work was supported by the National Natural Science Foundation of China (81671437, 81771558) and the Natural Science Foundation of Hunan Province, China (2016JC2049, 2020JJ4814).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, NO.139 Middle Renmin Road, Changsha, 410011, Hunan, China

    Mingyu Yi, Sixue Wang, Xinyue Zhang, Li Jiang, Xiaomeng Xia, Tingting Zhang & Xiaoling Fang

Authors
  1. Mingyu Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sixue Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinyue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaomeng Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tingting Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaoling Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Mingyu Yi: Data curation, methodology, software, writing—original draft preparation. Sixue Wang: Data curation, Writing—Original draft preparation. Xinyue Zhang: Data curation, writing—original draft preparation. Li Jiang: Resources, Investigation, validation. Xiaomeng Xia: Resources, investigation, validation. Tingting Zhang: Resources, investigation, validation. Xiaoling Fang: Supervision, writing—reviewing and editing, funding acquisition.

Corresponding author

Correspondence to Xiaoling Fang.

Ethics declarations

Ethics Approval

This study was approved by the Institutional Ethics Review Committee of Second Xiangya Hospital of Central South University (#2016243).

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Fig. S1

Validation of transfection plasmid Linc-ROR, miR-204-5p mimic and miR-204-5p Inhibitor. a Plasmid map of Linc-ROR. b 1 μg plasmid Linc-ROR and vector was transfected into End1/E6E7 and Ishikawa cells respectively, and qRT-PCR was conducted to measure the relatively expression of Linc-ROR. Two-tailed Student’s t-test was conducted for statistical analysis. c 50 nM miR-204-5p mimic or mimic NC was transfected into End1/E6E7 and Ishikawa cells, 80 nM miR-204-5p Inhibitor or Inhibitor NC was transfected into Ishikawa cells, and 30 nM miR-204-5p Inhibitor or Inhibitor NC was transfected into End1/E6E7 cells, the transfection was confirmed using qRT-PCR. Two-tailed Student’s t-test was conducted for statistical analysis. E6E7, End1/E6E7; ISK, Ishikawa; mimic, miR-204-5p mimic; inhibitor, miR-204-5p Inhibitor; NC, natural control. (PNG 214 kb)

High resolution image (TIF 860 kb)

Fig. S2

Expression of miR-124-3p, miR-138-5p, miR-195-5p and miR-205-5p, and their regulation by Linc-ROR. a-d Left panel shows expression levels of miR-124-3p, miR-138-5p, miR-195-5p and miR-205-5p in ectopic endometrium (EC, n = 10), eutopic endometrium (EU, n = 10), and control group (NC, n = 10) by qRT-PCR. Kruskal–Wallis test followed by pot-hoc Dunn’s test was conducted for statistical analysis. Right panel shows expression of miR-124-3p, miR-138-5p, miR-195-5p and miR-205-5p in End1/E6E7 and Ishikawa cells transfected with Linc-ROR plasmid or control vector using qRT-PCR. Two-tailed Student’s t-test was conducted for statistical analysis. E6E7, End1/E6E7; ISK, Ishikawa. (PNG 236 kb)

High resolution image (TIF 1273 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yi, M., Wang, S., Zhang, X. et al. Linc-ROR Promotes EMT by Targeting miR-204-5p/SMAD4 in Endometriosis. Reprod. Sci. 30, 2665–2679 (2023). https://doi.org/10.1007/s43032-023-01204-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-023-01204-0

Keywords

Search

Navigation