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Current Pharmaceutical Biotechnology

Author(s): Robert Nowakowski*, Beniamin Grabarek, Anna Burnat-Olech, Dariusz Boroń and Monika Paul-Samojedny

DOI: 10.2174/1389201022666210702153919

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Variances in the Expression Profile of the EMT-Related Genes in Endometrial Cancer Lines In Vitro Study

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Abstract

Background: The aim of the study was to evaluate the variances in the expression pattern of mRNAs and miRNAs related to the EMT in the Ishikawa (histological grade 1; G1), EC-1A (histological grade 2; G2), and KLE (histological grade 3; G3) cell cultures under cisplatin treatment.

Methods: Endometrial cancer cell lines were exposed to 75.22 mg (an average concentration of the drug used in patients with endometrial cancer) for 12.24 and 48 hours in comparison to the untreated cells (control). The molecular analysis included: extraction of total RNA, microarray analysis (mRNA and miRNA), RTqPCR, and the ELISA assay.

Results: Out of 226 mRNAs associated with the EMT, the number of mRNAs differentially expressed in endometrial cancer cell cultures treated with cisplatin compared to a control culture was as follows: Ishikawa line - 87 mRNAs; EC-1A - 84 mRNAs; KLE - 71 mRNAs (p<0.05). The greatest changes in the Ishikawa line treated with the drug compared to the control were noticed for mRNA STAT1 TGFβ1, SMAD3, FOXO8, whereas in EC-1A they were mRNA TGFβ1, BAMBI, SMAD4, and in KLE mRNA COL1A1, FOXO8, TGFβ1. The analysis also showed that miR-106a, miR-30d, miR-300 are common for all cell lines used in this experiment.

Conclusion: Cisplatin changes the expression profile of genes associated with EMT in endometrial cancer cell lines. It seems that the expression pattern of TGFβ1 might be a promising, supplementary molecular marker of the effectiveness of cisplatin therapy. The analysis showed that miR-30d, miR-300, and miR-106a are involved in the regulation of the expression of EMT-related genes.

Keywords: Cisplatin, endometrial cancer, cell line, mRNA, miRNA, epithelial-mesenchymal transition.

Graphical Abstract

[1]
Raglan, O.; Kalliala, I.; Markozannes, G.; Cividini, S.; Gunter, M.J.; Nautiyal, J.; Gabra, H.; Paraskevaidis, E.; Martin-Hirsch, P.; Tsilidis, K.K.; Kyrgiou, M. Risk factors for endometrial cancer: An umbrella review of the literature. Int. J. Cancer, 2019, 145(7), 1719-1730.
[http://dx.doi.org/10.1002/ijc.31961] [PMID: 30387875]
[2]
Onstad, M.A.; Schmandt, R.E.; Lu, K.H. Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. JCM, 2016, 34(35), 4225.
[3]
Forsse, D.; Tangen, I.L.; Fasmer, K.E.; Halle, M.K.; Viste, K.; Almås, B.; Bertelsen, B.E.; Trovik, J.; Haldorsen, I.S.; Krakstad, C. Blood steroid levels predict survival in endometrial cancer and reflect tumor estrogen signaling. Gynecol. Oncol., 2020, 156(2), 400-406.
[http://dx.doi.org/10.1016/j.ygyno.2019.11.123] [PMID: 31813586]
[4]
Mørch, L.S.; Kjaer, S.K.; Keiding, N.; Løkkegaard, E.; Lidegaard, Ø. The influence of hormone therapies on type I and II endometrial cancer: A nationwide cohort study. Int. J. Cancer, 2016, 138(6), 1506-1515.
[http://dx.doi.org/10.1002/ijc.29878] [PMID: 26421912]
[5]
Sznurkowski, J.J.; Knapp, P.; Bodnar, L.; Bidziński, M.; Jach, R.; Misiek, M.; Markowska, J. Zalecenia Polskiego Towarzystwa Ginekologii Onkologicznej dotyczące diagnostyki i leczenia raka endometrium. Curr. Gynecol. Oncol., 2017, 15(1), 34-44.
[http://dx.doi.org/10.15557/CGO.2017.0003]
[6]
Mang, C.; Birkenmaier, A.; Cathomas, G.; Humburg, J. Endometrioid endometrial adenocarcinoma: An increase of G3 cancers? Arch. Gynecol. Obstet., 2017, 295(6), 1435-1440.
[http://dx.doi.org/10.1007/s00404-017-4370-4] [PMID: 28421274]
[7]
Koyuncu, K.; Altın, D.; Turgay, B.; Varlı, B.; Konuralp, B.; Şükür, Y.E.; Ortaç, F. Binary grading may be more appropriate for endo-metrial cancer. J. Turk. Ger. Gynecol. Assoc., 2020, 21(3), 163.
[8]
Devor, E.J.; Gonzalez-Bosquet, J.; Thiel, K.W.; Leslie, K.K. Genomic characterization of five commonly used endometrial cancer cell lines. Int. J. Oncol., 2020, 57(6), 1348-1357.
[http://dx.doi.org/10.3892/ijo.2020.5139] [PMID: 33174010]
[9]
Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(2), 69-84.
[http://dx.doi.org/10.1038/s41580-018-0080-4] [PMID: 30459476]
[10]
Yeung, K.T.; Yang, J. Epithelial-mesenchymal transition in tumor metastasis. Mol. Oncol., 2017, 11(1), 28-39.
[http://dx.doi.org/10.1002/1878-0261.12017] [PMID: 28085222]
[11]
Song, J.; Wang, W.; Wang, Y.; Qin, Y.; Wang, Y.; Zhou, J.; Wang, Q. Epithelial-mesenchymal transition markers screened in a cell-based model and validated in lung adenocarcinoma. BMC Cancer, 2019, 19(1), 680.
[http://dx.doi.org/10.1186/s12885-019-5885-9]
[12]
Zhu, G.J.; Song, P.P.; Zhou, H.; Shen, X.H.; Wang, J.G.; Ma, X.F.; Gu, Y.J.; Liu, D.D.; Feng, A.N.; Qian, X.Y.; Gao, X. Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, β-catenin and ZEB2 in laryngeal squamous cell carcinoma. Oncol. Lett., 2018, 15(3), 3472-3481.
[http://dx.doi.org/10.3892/ol.2018.7751] [PMID: 29467869]
[13]
Du, B.; Shim, J.S. Targeting epithelial–mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules, 2016, 21(7), 965.
[14]
Tanabe, S.; Quader, S.; Cabral, H.; Ono, R. Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Front. Pharmacol., 2020, 11, 904.
[http://dx.doi.org/10.3389/fphar.2020.00904] [PMID: 32625096]
[15]
Mi, H.; Muruganujan, A.; Ebert, D.; Huang, X.; Thomas, P.D. PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res., 2019, 47(D1), D419-D426.
[http://dx.doi.org/10.1093/nar/gky1038] [PMID: 30407594]
[16]
Aiello, N.M.; Kang, Y. Context-dependent EMT programs in cancer metastasis. J. Exp. Med., 2019, 216(5), 1016-1026.
[http://dx.doi.org/10.1084/jem.20181827] [PMID: 30975895]
[17]
Lu, T.X.; Rothenberg, M.E. MicroRNA. J. Allergy Clin. Immunol., 2018, 141(4), 1202-1207.
[http://dx.doi.org/10.1016/j.jaci.2017.08.034] [PMID: 29074454]
[18]
Mathew, R.; Mattei, V.; Al Hashmi, M.; Tomei, S. Updates on the current technologies for microRNA Profiling. MicroRNA, 2020, 9(1), 17-24.
[http://dx.doi.org/10.2174/2211536608666190628112722] [PMID: 31264553]
[19]
Ahadi, A. A systematic review of microRNAs as potential biomarkers for diagnosis and prognosis of gastric cancer. Immunogenetics, 2021, 73(2), 155-161.
[http://dx.doi.org/10.1007/s00251-020-01201-6] [PMID: 33399935]
[20]
Ramanathan, K.; Padmanabhan, G. MiRNAs as potential biomarker of kidney diseases: A review. Cell Biochem. Funct., 2020, 38(8), 990-1005.
[http://dx.doi.org/10.1002/cbf.3555] [PMID: 32500596]
[21]
Abdalla, M.; Deshmukh, H.; Atkin, S.L.; Sathyapalan, T. miRNAs as a novel clinical biomarker and therapeutic targets in polycystic ovary syndrome (PCOS): A review. Life Sci., 2020, 259 ,118174.
[http://dx.doi.org/10.1016/j.lfs.2020.118174] [PMID: 32745529]
[22]
Vamanu, E. Polyphenolic nutraceuticals to combat oxidative stress through microbiota modulation. Front. Pharmacol., 2019, 10, 492.
[http://dx.doi.org/10.3389/fphar.2019.00492] [PMID: 31130865]
[23]
Vamanu, E. Complementary Functional Strategy for Modulation of Human Gut Microbiota. Curr. Pharm. Des., 2018, 24(35), 4144-4149.
[http://dx.doi.org/10.2174/1381612824666181001154242] [PMID: 30277147]
[24]
Walther-António, M.R.; Chen, J.; Multinu, F.; Hokenstad, A.; Distad, T.J.; Cheek, E.H.; Keeney, G.L.; Creedon, D.J.; Nelson, H.; Mariani, A.; Chia, N. Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome Med., 2016, 8(1), 122.
[http://dx.doi.org/10.1186/s13073-016-0368-y] [PMID: 27884207]
[25]
Walsh, D.M.; Hokenstad, A.N.; Chen, J.; Sung, J.; Jenkins, G.D.; Chia, N.; Nelson, H.; Mariani, A.; Walther-Antonio, M.R.S. Post-menopause as a key factor in the composition of the Endometrial Cancer Microbiome (ECbiome). Sci. Rep., 2019, 9(1), 19213.
[http://dx.doi.org/10.1038/s41598-019-55720-8] [PMID: 31844128]
[26]
Lu, W.; He, F.; Lin, Z.; Liu, S.; Tang, L.; Huang, Y.; Hu, Z. Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer. Int. J. Cancer, 2021, 148(7), 1708-1716.
[http://dx.doi.org/10.1002/ijc.33428] [PMID: 33285000]
[27]
Winters, A.D.; Romero, R.; Gervasi, M.T.; Gomez-Lopez, N.; Tran, M.R.; Garcia-Flores, V.; Pacora, P.; Jung, E.; Hassan, S.S.; Hsu, C.D.; Theis, K.R. Does the endometrial cavity have a molecular microbial signature? Sci. Rep., 2019, 9(1), 9905.
[http://dx.doi.org/10.1038/s41598-019-46173-0] [PMID: 31289304]
[28]
Koutsos, A.; Tuohy, K.M.; Lovegrove, J.A. Apples and cardiovascular health--is the gut microbiota a core consideration? Nutrients, 2015, 7(6), 3959-3998.
[http://dx.doi.org/10.3390/nu7063959] [PMID: 26016654]
[29]
Finimundy, T.C.; Gambato, G.; Fontana, R.; Camassola, M.; Salvador, M.; Moura, S.; Hess, J.; Henriques, J.A.; Dillon, A.J.; Roesch-Ely, M. Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity. Nutr. Res., 2013, 33(1), 76-84.
[http://dx.doi.org/10.1016/j.nutres.2012.11.005] [PMID: 23351413]
[30]
Hosseinimehr, S.J.; Pourmorad, F.; Shahabimajd, N.; Shahrbandy, K.; Hosseinzadeh, R. in vitro antioxidant activity of Polygonium hyrcanicum, Centaurea depressa, Sambucus ebulus, Mentha spicata and Phytolacca americana. Pak. J. Biol. Sci., 2007, 10(4), 637-640.
[http://dx.doi.org/10.3923/pjbs.2007.637.640] [PMID: 19069549]
[31]
Keshavarzian, D.A. Mutlu, E.A. complementary and alternative medicine in inflammatory bowel disease. Gastroenterol. Clin. North Am., 2017, 46, 4.
[32]
Joffe, Y.; Herholdt, H. What will it take to build an expert group of nutrigenomic practitioners? Lifestyle Genomics, 2020, 13(3), 122-128.
[http://dx.doi.org/10.1159/000507252] [PMID: 32369817]
[33]
Peszek, W.; Kras, P.; Grabarek, B.O.; Boroń, D.; Oplawski, M. Cisplatin changes expression of SEMA3B in endometrial cancer. Curr. Pharm. Biotechnol., 2020, 21(13), 1368-1376.
[http://dx.doi.org/10.2174/1389201021666200514215839] [PMID: 32410560]
[34]
Kieszkowski, P.; Dąbruś, D.; Grabarek, B.O.; Boroń, D. Differences in the expression pattern of mRNA protein SEMA3F in endometrial cancer in vitro under Cisplatin Treatment. Curr. Pharm. Biotechnol., 2020, 21(11), 1119-1128.
[http://dx.doi.org/10.2174/1389201021666200416102540] [PMID: 32297576]
[35]
Kiełabsiński, R.; Kieszkowski, P.; Grabarek, B.O.; Boroń, D. Evaluation of changes in the expression profile of mRNA and proteinencoding adiponectin in ishikawa cell line under the influence of cisplatin - preliminary report. Curr. Pharm. Biotechnol., 2020, 21(12), 1242-1248.
[http://dx.doi.org/10.2174/1389201021666200506074523] [PMID: 32370713]
[36]
Dąbruś, D.; Kiełbasiński, R.; Grabarek, B.O.; Boroń, D. Evaluation of the impact of cisplatin on variances in the expression pattern of leptin-related genes in endometrial cancer cells. Int. J. Mol. Sci., 2020, 20(11), 4135.
[37]
Makovec, T. Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiother. Oncol., 2019, 53(2), 148.
[http://dx.doi.org/10.2478/raon-2019-0018]
[38]
Basu, A.; Krishnamurthy, S. Cellular responses to cisplatin-induced DNA damage. J. Nucleic Acids, 2010.
[http://dx.doi.org/10.4061/2010/201367]
[39]
Siddik, Z.H. Biochemical and molecular mechanisms of cisplatin resistance; Clinically Relevant Resistance in Cancer Chemotherapy, 2002, pp. 263-284.
[http://dx.doi.org/10.1007/978-1-4615-1173-1_13]
[40]
Hanigan, M.H.; Devarajan, P. Cisplatin nephrotoxicity: Molecular mechanisms. Cancer Ther., 2003, 1, 47-61.
[PMID: 18185852]
[41]
Oplawski, M.; Dziobek, K.; Zmarzły, N.; Grabarek, B.O.; Kiełbasiński, R.; Kieszkowski, P.; Januszyk, P.; Talkowski, K.; Schweizer, M.; Kras, P.; Plewka, A.; Boroń, D. Variances in the level of COX-2 and iNOS in different grades of endometrial cancer. Curr. Pharm. Biotechnol., 2020, 21(1), 52-59.
[http://dx.doi.org/10.2174/1389201020666190918104105] [PMID: 31533599]
[42]
Kiełbasiński, K.; Peszek, W.; Grabarek, B.O.; Boroń, D.; Wierzbik-Strońska, M.; Oplawski, M. Effect of salinomycin on expression pattern of genes associated with apoptosis in endometrial cancer cell line. Curr. Pharm. Biotechnol., 2020, 21(12), 1269-1277.
[http://dx.doi.org/10.2174/1389201021666200513074022] [PMID: 32400328]
[43]
Hsu, J.B.K.; Chiu, C.M.; Hsu, S.D.; Huang, W.Y.; Chien, C.H.; Lee, T.Y.; Huang, H.D. miRTar: An integrated system for identifying miRNA-target interactions in human. BMC Bioinformatics, 2011, 12(1), 300.
[44]
Saeid, M.M.; Nossair, Z.B.; Saleh, M.A. A microarray cancer classification technique based on discrete wavelet transform for data reduction and genetic algorithm for feature selection. 4th International Conference on Trends in Electronics and Informatics (ICOEI), 2020, pp. 857-861.
[45]
Grabarek, B.; Wcisło-Dziadecka, D.; Strzałka-Mrozik, B.; Adamska, J.; Mazurek, U.; Brzezińska-Wcisło, L. The capability to forecast response to therapy with regard to the time and intensity of the inflammatory process in vitro in Dermal Fibroblasts Induced by IL-12. Curr. Pharm. Biotechnol., 2018, 19(15), 1232-1240.
[http://dx.doi.org/10.2174/1389201020666190111163312] [PMID: 30636601]
[46]
Kurnit, K.C.; Bailey, A.M.; Zeng, J.; Johnson, A.M.; Shufean, M.A.; Brusco, L.; Litzenburger, B.C.; Sánchez, N.S.; Khotskaya, Y.B.; Holla, V.; Simpson, A.; Mills, G.B.; Mendelsohn, J.; Bernstam, E.; Shaw, K.; Meric-Bernstam, F.; Simpson, A. Personalized cancer therapy: A publicly available precision oncology resource. Cancer Res., 2017, 77(21), e123-e126.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0341] [PMID: 29092956]
[47]
Groenland, S.L.; Mathijssen, R.H.J.; Beijnen, J.H.; Huitema, A.D.R.; Steeghs, N. Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine. Eur. J. Clin. Pharmacol., 2019, 75(9), 1309-1318.
[http://dx.doi.org/10.1007/s00228-019-02704-2] [PMID: 31175385]
[48]
Bhola, N.E.; Balko, J.M.; Dugger, T.C.; Kuba, M.G.; Sánchez, V.; Sanders, M.; Stanford, J.; Cook, R.S.; Arteaga, C.L. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. J. Clin. Invest., 2013, 123(3), 1348-1358.
[http://dx.doi.org/10.1172/JCI65416] [PMID: 23391723]
[49]
Bandyopadhyay, A.; Wang, L.; Agyin, J.; Tang, Y.; Lin, S.; Yeh, I.T.; De, K.; Sun, L.Z. Doxorubicin in combination with a small TGFbeta inhibitor: A potential novel therapy for metastatic breast cancer in mouse models. PLoS One, 2010, 5(4) ,e10365.
[http://dx.doi.org/10.1371/journal.pone.0010365] [PMID: 20442777]
[50]
Zhu, H.; Gu, X.; Xia, L.; Zhou, Y.; Bouamar, H.; Yang, J.; Ding, X.; Zwieb, C.; Zhang, J.; Hinck, A.P.; Sun, L.Z.; Zhu, X. A Novel TGFβ trap blocks chemotherapeutics-induced TGFβ1 signaling and enhances their anticancer activity in gynecologic cancers. Clin. Cancer Res., 2018, 24(12), 2780-2793.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3112] [PMID: 29549162]
[51]
Chen, L.; Yang, T.; Lu, D.W.; Zhao, H.; Feng, Y.L.; Chen, H.; Chen, D.Q.; Vaziri, N.D.; Zhao, Y.Y. Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment. Biomed. Pharmacother., 2018, 101, 670-681.
[http://dx.doi.org/10.1016/j.biopha.2018.02.090] [PMID: 29518614]
[52]
Dobrogowski, J.; Przeklasa-Muszyńska, A.; Woroń, J.; Wordliczek, J. Zasady kojarzenia leków w terapii bólu.Palliat. Care, 2007, 11-, 6-15.
[53]
Huang, X.; Wang, X.; Shang, J.; Zhaang, Z.; Cui, B.; Lin, Y.; Yang, Y.; Song, Y.; Yu, S.; Xia, J. Estrogen related receptor alpha triggers the migration and invasion of endometrial cancer cells via up regulation of TGFB1. Cell Adhes. Migr., 2018, 12(6), 538-547.
[http://dx.doi.org/10.1080/19336918.2018.1477901] [PMID: 29781387]
[54]
Katsuno, Y.; Lamouille, S.; Derynck, R. TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr. Opin. Oncol., 2013, 25(1), 76-84.
[http://dx.doi.org/10.1097/CCO.0b013e32835b6371] [PMID: 23197193]
[55]
Katsuno, Y.; Meyer, D.S.; Zhang, Z.; Shokat, K.M.; Akhurst, R.J.; Miyazono, K.; Derynck, R. Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition. Sci. Signal., 2019, 12(570), 8544.
[http://dx.doi.org/10.1126/scisignal.aau854]
[56]
Yeh, H.W.; Hsu, E.C.; Lee, S.S.; Lang, Y.D.; Lin, Y.C.; Chang, C.Y.; Lee, S.Y.; Gu, D.L.; Shih, J.H.; Ho, C.M.; Chen, C.F.; Chen, C.T.; Tu, P.H.; Cheng, C.F.; Chen, R.H.; Yang, R.B.; Jou, Y.S. PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis. Nat. Cell Biol., 2018, 20(4), 479-491.
[http://dx.doi.org/10.1038/s41556-018-0062-y] [PMID: 29593326]
[57]
Li, X.; Feng, X.H. SMAD-oncoprotein interplay: Potential determining factors in targeted therapies. Biochem. Pharmacol., 2020, 180 ,114155.
[http://dx.doi.org/10.1016/j.bcp.2020.114155] [PMID: 32682760]
[58]
Ma, T.T.; Meng, X.M. TGF-β/Smad and renal fibrosis.Renal Fibrosis; Mechanisms and Therapies Springer: Singapore, 2019, pp. 347-364.
[http://dx.doi.org/10.1007/978-981-13-8871-2_16]
[59]
Luo, K. Signaling cross talk between TGF-β/Smad and other signaling pathways. Cold Spring Harb. Perspect. Biol., 2017, 9(1) ,a022137.
[http://dx.doi.org/10.1101/cshperspect.a022137] [PMID: 27836834]
[60]
Zeng, X.; Baba, T.; Hamanishi, J.; Matsumura, N.; Kharma, B.; Mise, Y.; Abiko, K.; Yamaguchi, K.; Horikawa, N.; Hunstman, D.G.; Mulati, K.; Kitamura, S.; Taki, M.; Murakami, R.; Hosoe, Y.; Mandai, M. Phosphorylation of STAT1 serine 727 enhances platinum resistance in uterine serous carcinoma. Int. J. Cancer, 2019, 145(6), 1635-1647.
[http://dx.doi.org/10.1002/ijc.32501] [PMID: 31228268]
[61]
Grabarek, B.; Wcislo-Dziadecka, D.; Gola, J.; Kruszniewska-Rajs, C.; Brzezinska-Wcislo, L.; Zmarzly, N.; Mazurek, U. Changes in the expression profile of Jak/Stat signaling pathway genes and miRNAs regulating their expression under the adalimumab therapy. Curr. Pharm. Biotechnol., 2018, 19(7), 556-565.
[http://dx.doi.org/10.2174/1389201019666180730094046] [PMID: 30058482]
[62]
Zhang, J.; Wang, F.; Liu, F.; Xu, G. Predicting STAT1 as a prognostic marker in patients with solid cancer. Ther. Adv. Med. Oncol., 2020, 12 ,1758835920917558.
[http://dx.doi.org/10.1177/1758835920917558] [PMID: 32426049]
[63]
Liang, D.; Song, Z.; Liang, W.; Li, Y.; Liu, S. Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK/ERK1/2 signalling. Nephrology (Carlton), 2019, 24(4), 481-488.
[http://dx.doi.org/10.1111/nep.13430] [PMID: 29934960]
[64]
Chen, W.; Huang, X.; Peng, A.; Chen, T.; Yang, R.; Huang, Y.; Xi, S. Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF-β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats. Evid. Based Complement. Alternat. Med., 2019, 7, 1-11.
[65]
Zhang, B.; Chen, X.; Xie, C.; Chen, Z.; Liu, Y.; Ru, F.; He, Y. Leptin promotes epithelial-mesenchymal transition in benign prostatic hyperplasia through downregulation of BAMBI. Exp. Cell Res., 2020, 387(1) ,111754.
[http://dx.doi.org/10.1016/j.yexcr.2019.11175]
[66]
Ma, H.P.; Chang, H.L.; Bamodu, O.A.; Yadav, V.K.; Huang, T.Y.; Wu, A.T. Collagen 1A1 (COL1A1) is a reliable biomarker and putative therapeutic target for hepatocellular carcinogenesis and metastasis. Cancers, 2019, 11(6), 786.
[67]
Li, M.; Wang, J.; Wang, C.; Xia, L.; Xu, J.; Xie, X.; Lu, W. Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis. Exp. Cell Res., 2020, 394(1) ,112153.
[http://dx.doi.org/10.1016/j.yexcr.2020.112153]
[68]
Expósito-Villén, A.E.; Aránega, A.; Franco, D. Functional role of non-coding RNAs during epithelial-to-mesenchymal transition. Noncoding RNA, 2018, 4(2), 14.
[http://dx.doi.org/10.3390/ncrna4020014]
[69]
Ye, Z.; Zhao, L.; Li, J.; Chen, W.; Li, X. miR-30d blocked transforming growth factor β1-induced epithelial-mesenchymal transition by targeting snail in ovarian cancer cells. Int. J. Gynecol. Cancer, 2015, 25(9), 1574-1581.
[http://dx.doi.org/10.1097/IGC.0000000000000546] [PMID: 26501435]
[70]
Cui, K.; Bian, X. The microRNA cluster miR-30b/-30d prevents tumor cell switch from an epithelial to a mesenchymal-like phenotype in GBC. Mol. Ther. Methods Clin. Dev., 2020, 20, 716-725.
[http://dx.doi.org/10.1016/j.omtm.2020.11.019] [PMID: 33738326]
[71]
Song, K.; Jiang, Y.; Zhao, Y.; Xie, Y.; Zhou, J.; Yu, W.; Wang, Q. Members of the miR-30 family inhibit the epithelial-to-mesenchymal transition of non-small-cell lung cancer cells by suppressing XB130 expression levels. Oncol. Lett., 2020, 20(4), 68.
[http://dx.doi.org/10.3892/ol.2020.11929] [PMID: 32863901]
[72]
Cai, J.L.; Liu, L.L.; Hu, Y.; Jiang, X.M.; Qiu, H.L.; Sha, A.G.; Wang, C.G.; Zuo, Z.H.; Ren, J.Z. Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition. Toxicology, 2016, 365, 25-34.
[http://dx.doi.org/10.1016/j.tox.2016.07.017] [PMID: 27481218]
[73]
Liu, J.D.; Xin, Q.; Tao, C.S.; Sun, P.F.; Xu, P.; Wu, B.; Qu, L.; Li, S.Z. Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma. Oncol. Lett., 2016, 12(5), 3912-3918.
[http://dx.doi.org/10.3892/ol.2016.5214] [PMID: 27895748]
[74]
Raji, G.R.; Sruthi, T.V.; Edatt, L.; Haritha, K.; Sharath Shankar, S.; Sameer Kumar, V.B. Horizontal transfer of miR-106a/b from cisplatin resistant hepatocarcinoma cells can alter the sensitivity of cervical cancer cells to cisplatin. Cell. Signal., 2017, 38, 146-158.
[http://dx.doi.org/10.1016/j.cellsig.2017.07.005] [PMID: 28709644]
[75]
Shi, B.; Ma, C.; Liu, G.; Guo, Y. MiR-106a directly targets LIMK1 to inhibit proliferation and EMT of oral carcinoma cells. Cell. Mol. Biol. Lett., 2019, 24(1), 1-14.
[http://dx.doi.org/10.1186/s11658-018-0127-8] [PMID: 30873211]
[76]
Stavast, C.J.; Erkeland, S.J. The non-canonical aspects of MicroRNAs: Many roads to gene regulation. Cells, 2019, 8(11), 8-11.1465.
[http://dx.doi.org/10.3390/cells8111465] [PMID: 31752361]