MicroRNA-122 Is More Effective than Rapamycin in Inhibition of Epithelial-mesenchymal Transition and mTOR Signaling Pathway in Triple Negative Breast Cancer
-
Majdedin Ghalavand
,
Ruhollah Dorostkar
,
Hojat Borna
,
Samira Mohammadi-Yeganeh
,
Seyed Mahmood Hashemi
Abstract
The fundamental mechanism responsible for the aggressiveness of metastatic cancers such as triple-negative breast cancer (TNBC) is the epithelial-mesenchymal transition (EMT). In cancer microenvironments, the Phosphoinositide 3-kinases (PI3K)-Akt- mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating the EMT mechanism. The current study focuses on the impacts of rapamycin, a newly retargeted chemotherapeutic agent against mTOR, and MicroRNA (miR)-122 on the aggressive behavior of TNBC.
The half-maximal inhibitory concentration (IC50) of rapamycin on 4T1 cells was determined using an MTT assay. Also, miR-122 was transiently transfected into 4T1 cells to study its effect on the pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression level of central mTOR and EMT-related cascade genes. Moreover, cell mobility and migration were evaluated using scratch and migration assays, respectively.
Both rapamycin and miR-122 significantly decreased the expression levels of PI3K, AKT, and mTOR, as well as ZeB1 and Snail genes. However, no significant change was observed in Twist gene expression. Furthermore, scratch and migration assays revealed that the migration of 4T1 cells was markedly reduced, especially following miR-122 induction. Our experimental findings and gene enrichment studies indicated that miR-122 mainly operates on multiple metabolic pathways, as well as EMT and mTOR, while rapamycin has restricted targets in cancer cells.
Consequently, miR-122 can be considered a potential cancer microRNA therapy option, which can be validated in the future in animal studies to demonstrate its efficacy in cancer control.
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25. Zhang YJ, Duan Y, Zheng XF. Targeting the mTOR kinase domain: the second generation of mTOR inhibitors. Drug Discov today. 2011;16(7-8):325-31.
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29. Saiyed AN, Vasavada AR, Johar SRK. Recent trends in miRNA therapeutics and the application of plant miRNA for prevention and treatment of human diseases. Future J Pharmaceutical Sci. 2022;8(1):24.
30. Khazaei-Poul Y, Shojaei S, Koochaki A, Ghanbarian H, Mohammadi-Yeganeh S. Evaluating the influence of Human Umbilical Cord Mesenchymal Stem Cells-derived exosomes loaded with miR-3182 on metastatic performance of Triple Negative Breast Cancer cells. Life sciences. 2021;286:120015.
31. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease? Trans Res. 2011;157(4):253-64.
32. Karami F, Mohammadi-Yeganeh S, Abedi N, Koochaki A, Kia V, Paryan M. Bioinformatics Prediction and In Vitro Analysis Revealed That miR-17 Targets Cyclin D1 mRNA in Triple Negative Breast Cancer Cells. Chem Biol Drug Des. 2016;87(3):317-20.
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34. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12(2):106.
35. Singh S, Lee N, Pedroza DA, Bado IL, Hamor C, Zhang L, et al. chemotherapy Coupled to Macrophage Inhibition Induces T-cell and B-cell Infiltration and Durable Regression in Triple-Negative Breast Cancer. Cancer Res. 2022;82(12):2281-97.
36. Dey P, Rathod M, De A. Targeting stem cells in the realm of drug-resistant breast cancer. Breast Cancer (Dove Med Press). 2019;11:115.
37. Sato R, Semba T, Saya H, Arima Y. Concise review: stem cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem cells. 2016;34(8):1997-2007.
38. Newton EE, Mueller LE, Treadwell SM, Morris CA, Machado HL. Molecular Targets of Triple-Negative Breast Cancer: Where Do We Stand? Cancers. 2022;14(3):482.
39. Zambelli A, Sgarra R, De Sanctis R, Agostinetto E, Santoro A, Manfioletti G. Heterogeneity of triple negative breast cancer: Understanding the daedalian labyrinth and how it could reveal new drug targets. Exp Opin Therapeutic Targets. 2022(just-accepted).
40. Costa RLB, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review. Breast Cancer Res Treat. 2018;169(3):397-406.
41. Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM. Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Clin Cancer Res. 2017;23(13):3405-15.
42. Chalakur-Ramireddy NKR, Pakala SB. Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer. Biosci Rep. 2018;38(1).
43. Mir MA, Qayoom H, Mehraj U, Nisar S, Bhat B, Wani NA. Targeting different pathways using novel combination therapy in triple negative breast Cancer. Curr Cancer Drug Targets. 2020;20(8):586-602.
44. Lee Y-N, Han Y-h, Kim W-S, Lee C-M, Moon E-J, Kim H-J. A promising combination partner for paclitaxel in triple-negative breast cancer (TNBC) therapy. Cancer Res. 2022;82(12_Supplement):5304.
45. Chandimali N, Huynh DL, Zhang JJ, Lee JC, Yu DY, Jeong DK, et al. MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells. Cancer Gene Ther. 2019;26(9-10):292-304.
46. Zong H, Yin B, Zhou H, Cai D, Ma B, Xiang Y. Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition. Mol Biol Rep. 2014;41(7):4507-12.
47. Aguilera A, Aroeira LS, Ramirez-Huesca M, Perez-Lozano ML, Cirugeda A, Bajo MA, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells. Int J Artif Organs. 2005;28(2):164-9.
48. Chahal J, Gebert LFR, Camargo C, MacRae IJ, Sagan SM. miR-122–based therapies select for three distinct resistance mechanisms based on alterations in RNA structure. Proc Natl Acad Sci U S A. 2021;118(33):e2103671118.
49. Meng L, Chen Z, Jiang Z, Huang T, Hu J, Luo P, et al. miR-122-5p suppresses the proliferation, migration, and invasion of gastric cancer cells by targeting LYN. Acta Biochim Biophys Sin (Shanghai). 2020;52(1):49-57.
50. Xu X, Gao F, Wang J, Tao L, Ye J, Ding L, et al. miR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4. Cancer Biol Ther. 2018;19(5):427-35.
51. Yang Y, Liu Y, Liu W, Li C, Liu Y, Hu W, et al. miR-122 Inhibits the Cervical Cancer Development by Targeting the Oncogene RAD21. Biochemical Gen. 2022;60(1):303-14.
52. Dai C, Zhang Y, Xu Z, Jin M. MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma. Cancer cell international. 2020;20:98.
53. Wang Y, Xing QF, Liu XQ, Guo ZJ, Li CY, Sun G. miR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis. Am J Transl Res. 2016;8(7):3056-66.
54. Li KW, Wang SH, Wei X, Hou YZ, Li ZH. Mechanism of miR-122-5p regulating the activation of PI3K-Akt-mTOR signaling pathway on the cell proliferation and apoptosis of osteosarcoma cells through targeting TP53 gene. Eur Rev Med Pharmacol Sci. 2020;24(24):12655-66.
55. Wang B, Wang H, Yang Z. miR-122 inhibits cell proliferation and tumorigenesis of breast cancer by targeting IGF1R. 2012.
56. Duan Y, Dong Y, Dang R, Hu Z, Yang Y, Hu Y, et al. miR‐122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells. Cell Biology Inter. 2018;42(11):1564-74.
57. Li H, Zhang X, Jin Z, Yin T, Duan C, Sun J, et al. miR-122 promotes the development of colon cancer by targeting ALDOA in vitro. Technol Cancer Res Treat. 2019;18:1533033819871300.
58. Jingushi K, Kashiwagi Y, Ueda Y, Kitae K, Hase H, Nakata W, et al. High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin. Int J Oncol. 2017;51(1):289-97.
59. Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17(2):183-94.
60. Thakral S, Ghoshal K. miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther. 2015;15(2):142-50.
61. Wang Z, Zhou J, Fan J, Qiu S-J, Yu Y, Huang X-W, et al. Effect of Rapamycin Alone and in Combination with Sorafenib in an Orthotopic Model of Human Hepatocellular Carcinoma. Clin Cancer Res. 2008;14(16):5124-30.
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2. Ashrafizadeh M, Zarrabi A, Hushmandi K, Kalantari M, Mohammadinejad R, Javaheri T, et al. Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance. Int J Mol Sciences. 2020;21(11).
3. Oualla K, El-Zawahry HM, Arun B, Reuben JM, Woodward WA, Gamal El-Din H, et al. Novel therapeutic strategies in the treatment of triple-negative breast cancer. Ther Adv Med Oncol. 2017;9(7):493-511.
4. Zhang J, Tian Q, Zhang M, Wang H, Wu L, Yang J. Immune-related biomarkers in triple-negative breast cancer. Breast cancer (Tokyo, Japan). 2021;28(4):792-805.
5. Joseph JP, Harishankar MK, Pillai AA, Devi A. Hypoxia induced EMT: A review on the mechanism of tumor progression and metastasis in OSCC. Oral oncology. 2018;80:23-32.
6. Yao D, Dai C, Peng S. Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 2011;9(12):1608-20.
7. Tam SY, Wu VWC, Law HKW. Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond. Front Oncology. 2020;10:486.
8. Mitra A, Mishra L, Li S. EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget. 2015;6(13):10697-711.
9. Huang Z, Zhang Z, Zhou C, Liu L, Huang C. Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities. Med Comm (2020). 2022;3(2):e144-e.
10. Prieto-García E, Díaz-García C, García-Ruiz I, Agulló-Ortuño MT. Epithelial-to-mesenchymal transition in tumor progression. Med Oncology. 2017;34.
11. Loh C-Y, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, et al. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells. 2019;8(10):1118.
12. Sha J, Bai Y, Ngo HX, Okui T, Kanno T. Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition. Biomolecules. 2021;11(6).
13. Khan MA, Jain VK, Rizwanullah M, Ahmad J, Jain K. PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a review on drug discovery and future challenges. Drug discovery today. 2019;24(11):2181-91.
14. Burgio SL, Fabbri F, Seymour IJ, Zoli W, Amadori D, De Giorgi U. Perspectives on mTOR inhibitors for castration-refractory prostate cancer. Curr Cancer Drug Targets. 2012;12(8):940-9.
15. Yu JS, Cui W. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development (Cambridge, England). 2016;143(17):3050-60.
16. Gao Y, Yuan CY, Yuan W. Will targeting PI3K/Akt/mTOR signaling work in hematopoietic malignancies? Stem cell Investigation. 2016;3:31.
17. Xu L, Zhang L, Hu C, Liang S, Fei X, Yan N, et al. WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncology. 2016;48(3):1175-86.
18. Wen Z, Feng S, Wei L, Wang Z, Hong D, Wang Q. Evodiamine, a novel inhibitor of the Wnt pathway, inhibits the self-renewal of gastric cancer stem cells. Int Journal Mol Med. 2015;36(6):1657-63.
19. Hseu Y-C, Huang Y-C, Korivi M, Wu J-J, Way T-D, Ou T-T, et al. Zerumbone attenuates TGF-β1-mediated epithelial–mesenchymal transition via upregulated E-cadherin expression and downregulated Smad2 signalling pathways in non-small cell lung cancer (A549) cells. J Functional foods. 2015;18:58-72.
20. Zhao L, Liu S, Che X, Hou K, Ma Y, Li C, et al. Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors. Int J Mol Med. 2015;36(3):645-52.
21. Han D, Wu G, Chang C, Zhu F, Xiao Y, Li Q, et al. Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway. Oncotarget. 2015;6(38):40907.
22. Namba T, Kodama R, Moritomo S, Hoshino T, Mizushima T. Zidovudine, an anti-viral drug, resensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine by inhibition of the Akt-GSK3β-Snail pathway. Cell Death Dis. 2015;6(6):e1795-e.
23. Xu B, Jiang C, Han H, Liu H, Tang M, Liu L, et al. Icaritin inhibits the invasion and epithelial‐to‐mesenchymal transition of glioblastoma cells by targeting EMMPRIN via PTEN/AKt/HIF‐1α signalling. Clin Exp Pharmacol Physiol. 2015;42(12):1296-307.
24. Jiang N, Dai Q, Su X, Fu J, Feng X, Peng J. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep. 2020;47(6):4587-629.
25. Zhang YJ, Duan Y, Zheng XF. Targeting the mTOR kinase domain: the second generation of mTOR inhibitors. Drug Discov today. 2011;16(7-8):325-31.
26. Teng QX, Ashar YV, Gupta P, Gadee E, Fan YF, Reznik SE, et al. Revisiting mTOR inhibitors as anticancer agents. Drug Discov Today. 2019;24(10):2086-95.
27. Abd-Aziz N, Kamaruzman NI, Poh CL. Development of MicroRNAs as Potential Therapeutics against Cancer. J Oncology. 2020;2020:8029721.
28. Hanna J, Hossain GS, Kocerha J. The Potential for microRNA Therapeutics and Clinical Research. Front Genetics. 2019;10:478.
29. Saiyed AN, Vasavada AR, Johar SRK. Recent trends in miRNA therapeutics and the application of plant miRNA for prevention and treatment of human diseases. Future J Pharmaceutical Sci. 2022;8(1):24.
30. Khazaei-Poul Y, Shojaei S, Koochaki A, Ghanbarian H, Mohammadi-Yeganeh S. Evaluating the influence of Human Umbilical Cord Mesenchymal Stem Cells-derived exosomes loaded with miR-3182 on metastatic performance of Triple Negative Breast Cancer cells. Life sciences. 2021;286:120015.
31. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease? Trans Res. 2011;157(4):253-64.
32. Karami F, Mohammadi-Yeganeh S, Abedi N, Koochaki A, Kia V, Paryan M. Bioinformatics Prediction and In Vitro Analysis Revealed That miR-17 Targets Cyclin D1 mRNA in Triple Negative Breast Cancer Cells. Chem Biol Drug Des. 2016;87(3):317-20.
33. Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. J Invest Dermatol. 2017;137(2):e11-e6.
34. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer Biol Med. 2015;12(2):106.
35. Singh S, Lee N, Pedroza DA, Bado IL, Hamor C, Zhang L, et al. chemotherapy Coupled to Macrophage Inhibition Induces T-cell and B-cell Infiltration and Durable Regression in Triple-Negative Breast Cancer. Cancer Res. 2022;82(12):2281-97.
36. Dey P, Rathod M, De A. Targeting stem cells in the realm of drug-resistant breast cancer. Breast Cancer (Dove Med Press). 2019;11:115.
37. Sato R, Semba T, Saya H, Arima Y. Concise review: stem cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem cells. 2016;34(8):1997-2007.
38. Newton EE, Mueller LE, Treadwell SM, Morris CA, Machado HL. Molecular Targets of Triple-Negative Breast Cancer: Where Do We Stand? Cancers. 2022;14(3):482.
39. Zambelli A, Sgarra R, De Sanctis R, Agostinetto E, Santoro A, Manfioletti G. Heterogeneity of triple negative breast cancer: Understanding the daedalian labyrinth and how it could reveal new drug targets. Exp Opin Therapeutic Targets. 2022(just-accepted).
40. Costa RLB, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review. Breast Cancer Res Treat. 2018;169(3):397-406.
41. Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa AA, Goldenberg DM. Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer. Clin Cancer Res. 2017;23(13):3405-15.
42. Chalakur-Ramireddy NKR, Pakala SB. Combined drug therapeutic strategies for the effective treatment of Triple Negative Breast Cancer. Biosci Rep. 2018;38(1).
43. Mir MA, Qayoom H, Mehraj U, Nisar S, Bhat B, Wani NA. Targeting different pathways using novel combination therapy in triple negative breast Cancer. Curr Cancer Drug Targets. 2020;20(8):586-602.
44. Lee Y-N, Han Y-h, Kim W-S, Lee C-M, Moon E-J, Kim H-J. A promising combination partner for paclitaxel in triple-negative breast cancer (TNBC) therapy. Cancer Res. 2022;82(12_Supplement):5304.
45. Chandimali N, Huynh DL, Zhang JJ, Lee JC, Yu DY, Jeong DK, et al. MicroRNA-122 negatively associates with peroxiredoxin-II expression in human gefitinib-resistant lung cancer stem cells. Cancer Gene Ther. 2019;26(9-10):292-304.
46. Zong H, Yin B, Zhou H, Cai D, Ma B, Xiang Y. Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition. Mol Biol Rep. 2014;41(7):4507-12.
47. Aguilera A, Aroeira LS, Ramirez-Huesca M, Perez-Lozano ML, Cirugeda A, Bajo MA, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells. Int J Artif Organs. 2005;28(2):164-9.
48. Chahal J, Gebert LFR, Camargo C, MacRae IJ, Sagan SM. miR-122–based therapies select for three distinct resistance mechanisms based on alterations in RNA structure. Proc Natl Acad Sci U S A. 2021;118(33):e2103671118.
49. Meng L, Chen Z, Jiang Z, Huang T, Hu J, Luo P, et al. miR-122-5p suppresses the proliferation, migration, and invasion of gastric cancer cells by targeting LYN. Acta Biochim Biophys Sin (Shanghai). 2020;52(1):49-57.
50. Xu X, Gao F, Wang J, Tao L, Ye J, Ding L, et al. miR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4. Cancer Biol Ther. 2018;19(5):427-35.
51. Yang Y, Liu Y, Liu W, Li C, Liu Y, Hu W, et al. miR-122 Inhibits the Cervical Cancer Development by Targeting the Oncogene RAD21. Biochemical Gen. 2022;60(1):303-14.
52. Dai C, Zhang Y, Xu Z, Jin M. MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma. Cancer cell international. 2020;20:98.
53. Wang Y, Xing QF, Liu XQ, Guo ZJ, Li CY, Sun G. miR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis. Am J Transl Res. 2016;8(7):3056-66.
54. Li KW, Wang SH, Wei X, Hou YZ, Li ZH. Mechanism of miR-122-5p regulating the activation of PI3K-Akt-mTOR signaling pathway on the cell proliferation and apoptosis of osteosarcoma cells through targeting TP53 gene. Eur Rev Med Pharmacol Sci. 2020;24(24):12655-66.
55. Wang B, Wang H, Yang Z. miR-122 inhibits cell proliferation and tumorigenesis of breast cancer by targeting IGF1R. 2012.
56. Duan Y, Dong Y, Dang R, Hu Z, Yang Y, Hu Y, et al. miR‐122 inhibits epithelial mesenchymal transition by regulating P4HA1 in ovarian cancer cells. Cell Biology Inter. 2018;42(11):1564-74.
57. Li H, Zhang X, Jin Z, Yin T, Duan C, Sun J, et al. miR-122 promotes the development of colon cancer by targeting ALDOA in vitro. Technol Cancer Res Treat. 2019;18:1533033819871300.
58. Jingushi K, Kashiwagi Y, Ueda Y, Kitae K, Hase H, Nakata W, et al. High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin. Int J Oncol. 2017;51(1):289-97.
59. Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17(2):183-94.
60. Thakral S, Ghoshal K. miR-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Ther. 2015;15(2):142-50.
61. Wang Z, Zhou J, Fan J, Qiu S-J, Yu Y, Huang X-W, et al. Effect of Rapamycin Alone and in Combination with Sorafenib in an Orthotopic Model of Human Hepatocellular Carcinoma. Clin Cancer Res. 2008;14(16):5124-30.
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| Files | ||
| Issue | Vol 22 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i1.12006 | |
| Keywords | ||
| Cancer microenvironment MIRN122 microRNA, human Rapamycin Triple-negative breast cancer Signaling pathway | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Ghalavand M, Dorostkar R, Borna H, Mohammadi-Yeganeh S, Hashemi SM. MicroRNA-122 Is More Effective than Rapamycin in Inhibition of Epithelial-mesenchymal Transition and mTOR Signaling Pathway in Triple Negative Breast Cancer. Iran J Allergy Asthma Immunol. 2023;22(1):46-61.
