Linoleic Acid Modulates the Expression of Metastatic and Angiogenic Markers MMP-2 and Talin-2 in Gastric Cancer Cell Line MKN-45
-
Daniel Elieh-Ali-Komi
,
Tohid Kazemi
,
Najibeh Shekari
,
Parviz Farzamifar
,
Elham Eghbali
,
Behzad Mansoori
,
Behzad Baradaran
,
Masoud Shirmohamadi
Abstract
Background: Linoleic acid (LA) has modulatory effects on gastric cancer cell lines. This study aimed to investigate the effects of linoleic acid on the expression of metastatic and angiogenic molecular markers in gastric cancer cell line MKN-45.
Methods: In this study performed in Tabriz, Iran in 2021, MKN-45 cells were treated with LA in the presence or absence of docetaxel. Total RNA was extracted, and cDNA synthesized from the cells before and after treatment. The expression levels of Talin-2 and MMP-2 genes and mir-20, mir-30, mir-126, and mir-194, were determined by quantitative real-time PCR.
Results: LA treatment reduced the expression levels of mir-126, mir-194, mir-30, and MMP-2, while increased the expression levels of Talin-2 mRNA. Docetaxel treatment could decrease the expression levels of mir-20, Talin-2, and MMP-2 mRNA levels while increasing the expression levels of mir-126, mir-194, and mir-30. Additionally, the combined treatment of MKN-45 cells with LA and docetaxel could reduce the expression levels of mir-20 and mir-126 and increased the expression levels of mir-194, mir-30, Talin-2, and MMP-2 mRNAs.
Conclusion: Modulation of the expression levels of gastric cancer involved microRNAs, Talin-2, and MMP-2 may be a mechanism through which LA may exert its biological effects on GC cell line MKN-45. LA may have an antimetastatic effect by reducing the MMP-2 expression and pro-angiogenic effect through increasing Talin-2 expression levels.
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3. Kelley NS, Hubbard NE, Erickson KL (2007). Conjugated linoleic acid isomers and cancer. J Nutr, 137 (12):2599-607.
4. Elieh Ali Komi D, Shekari N, Soofian-kordkandi P, et al (2021). Docosahexaenoic acid (DHA) and linoleic acid (LA) modulate the expression of breast cancer involved miRNAs in MDA-MB-231 cell line. Clin Nutr ESPEN, 46:477-483.
5. Dai J, Shen J, Pan W, Shen S, et al (2013). Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro. Lipids Health Dis, 12:71.
6. Liu JR, Li BX, Chen BQ, et al (2002). Effect of cis-9, trans-11-conjugated linoleic acid on cell cycle of gastric adenocarcinoma cell line (SGC-7901). World J Gastroenterol, 8 (2):224-9.
7. Elahirad S, Elieh Ali Komi D, Kiani A, et al (2022). Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Polymorphisms, Their Serum Levels, and Activities with Coronary Artery Calcification (CAC) in an Iranian Population. Cardiovasc Toxicol, 22 (2):118-129.
8. Najafi K, Komi DEA, Khazaie H, et al (2018). Investigation of Serum Levels and Activity of Matrix Metalloproteinases 2 and 9 (MMP2, 9) in Opioid and Methamphetamine-Dependent Patients. Acta Med Iran, 56 (9):559-562.
9. Xie YL, Tao WH, Yang TX, et al (2016). Anticancer effect of cucurbitacin B on MKN-45 cells via inhibition of the JAK2/STAT3 signaling pathway. Exp Ther Med, 12 (4):2709-2715.
10. Yokozaki H (2000). Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int, 50 (10):767-77.
11. Soe ZY, Prajuabjinda O, Myint PK, et al (2019). Talin-2 regulates integrin functions in exosomes. Biochem Biophys Res Commun, 512 (3):429-434.
12. Mostmans Y, De Smedt K, Richert B, et al (2021). Markers for the involvement of endothelial cells and the coagulation system in chronic urticaria: A systematic review. Allergy, 76 (10):2998-3016.
13. Elieh Ali Komi D, Wöhrl S, Bielory L (2020). Mast Cell Biology at Molecular Level: a Comprehensive Review. Clin Rev Allergy Immunol, 58 (3):342-365.
14. Komi DEA, Redegeld FA (2020). Role of Mast Cells in Shaping the Tumor Microenvironment. Clin Rev Allergy Immunol, 58 (3):313-325.
15. Elieh Ali Komi D, Kuebler WM (2022). Significance of Mast Cell Formed Extracellular Traps in Microbial Defense. Clin Rev Allergy Immunol, 62(1):160-179.
16. Komi DEA, Khomtchouk K, Santa Maria PL (2020). A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms. Clin Rev Allergy Immunol, 58 (3):298-312.
17. Liu HN, Wu H, Tseng YJ, et al (2018). Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer. BMC Cancer, 18 (1):415.
18. Feng Q, Wu X, Li F, et al (2017). miR-27b inhibits gastric cancer metastasis by targeting NR2F2. Protein Cell, 8 (2):114-122.
19. Wang H, Wang G, Tian WL (2019). [MiR-126 inhibits the proliferation and invasion of gastric cancer by downregulation of IGF-1R]. Zhonghua Zhong Liu Za Zhi, 41 (7):508-515.
20. Feng R, Sah BK, Beeharry MK, et al (2018). Dysregulation of miR-126/Crk protein axis predicts poor prognosis in gastric cancer patients. Cancer Biomark, 21 (2):335-343.
21. Wang J, Jiao Y, Cui L, Jiang L (2017). miR-30 functions as an oncomiR in gastric cancer cells through regulation of P53-mediated mitochondrial apoptotic pathway. Biosci Biotechnol Biochem, 81 (1):119-126.
22. Peng Y, Zhang X, Lin H, et al (2018). Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer. Oncol Rep, 40 (6):3323-3334.
23. Bao J, Zou JH, Li CY, Zheng GQ (2016). miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B. Eur Rev Med Pharmacol Sci, 20 (21):4487-4493.
24. Yoshida K, Kodera Y, Kochi M, et al (2019). Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol, 37 (15):1296-1304.
25. Yamada Y, Boku N, Mizusawa J, et al (2019). Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol, 4 (7):501-510.
26. Mirabdaly S, Elieh Ali Komi D, Shakiba Y,et al(2020). Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties. Mol Biol Rep, 47 (2):1187-1197.
27. Shekari N, Asghari F, Haghnavaz N, et al (2019). Let-7a Could Serve as A Biomarker for Chemo-Responsiveness to Docetaxel in Gastric Cancer. Anticancer Agents Med Chem, 19 (3):304-309.
28. Sasaki T, Fujii K, Yoshida K, et al (2006). Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells. Virchows Arch, 448 (4):422-7.
29. Chen BQ, Xue YB, Liu JR, et al (2003). Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms. World J Gastroenterol, 9 (1):44-9.
30. Ohmori H, Sasahira T, Fujii K, Yi L, et al (2008). Linoleic-acid-induced growth suppression induces quiescent cancer cell nests in nude mice. Pathobiology, 75 (4):226-32.
31. Connolly JM, Liu XH, Rose DP (1996). Dietary linoleic acid-stimulated human breast cancer cell growth and metastasis in nude mice and their suppression by indomethacin, a cyclooxygenase inhibitor. Nutr Cancer, 25 (3):231-40.
32. Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, et al (2011). Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A. Int J Biochem Cell Biol, 43 (12):1782-91.
33. Yang Y, Chen B, Xue Y, Zheng Y (2003). [Effects of c9, t11-conjugated linoleic acid on the metastasis of human gastric carcinoma cell line]. Wei Sheng Yan Jiu, 32 (2):117-9.
34. Kwon JI, Kim GY, Park KY, et al (2008). Induction of apoptosis by linoleic acid is associated with the modulation of Bcl-2 family and Fas/FasL system and activation of caspases in AGS human gastric adenocarcinoma cells. J Med Food, 11 (1):1-8.
35. Choi YH (2014). Linoleic Acid-Induced Growth Inhibition of Human Gastric Epithelial Adenocarcinoma AGS Cells is Associated with Down-Regulation of Prostaglandin E2 Synthesis and Telomerase Activity. J Cancer Prev, 19 (1):31-8.
36. Puebla C, Cisterna BA, Salas DP, et al (2016). Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism. Biochim Biophys Acta, 1861 (5):439-48.
37. Kuniyasu H, Yoshida K, Sasaki T, et al (2006). Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. Int J Cancer, 118 (3):571-6.
38. Nishioka N, Matsuoka T, Yashiro M, et al (2011). Linoleic acid enhances angiogenesis through suppression of angiostatin induced by plasminogen activator inhibitor 1. Br J Cancer, 105 (11):1750-8.
39. Matsuoka T, Adair JE, Lih FB, et al (2010). Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice. Br J Cancer, 103 (8):1182-91.
40. Haghnavaz N, Asghari F, Elieh Ali Komi D, et al (2018). HER2 positivity may confer resistance to therapy with paclitaxel in breast cancer cell lines. Artif Cells Nanomed Biotechnol, 46 (3):518-523.
41. Alipoor SD, Chang H (2023). Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma. Cells, 12 (7):1030.
42. Parra P, Serra F, Palou A (2010). Expression of adipose microRNAs is sensitive to dietary conjugated linoleic acid treatment in mice. PLoS One, 5 (9):e13005.
43. Feng R, Beeharry MK, Lu S, et al (2018). Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer. Cancer Biomark, 22 (1):119-126.
44. Li Q, Wang G, Wang H (2018). MiR-126 functions as a tumor suppressor by targeting SRPK1 in human gastric cancer. Oncol Res, 26(9):1345-1353.
2. Chen BQ, Yang YM, Gao YH, et al (2003). Inhibitory effects of c9, t11-conjugated linoleic acid on invasion of human gastric carcinoma cell line SGC-7901. World J Gastroenterol, 9 (9):1909-14.
3. Kelley NS, Hubbard NE, Erickson KL (2007). Conjugated linoleic acid isomers and cancer. J Nutr, 137 (12):2599-607.
4. Elieh Ali Komi D, Shekari N, Soofian-kordkandi P, et al (2021). Docosahexaenoic acid (DHA) and linoleic acid (LA) modulate the expression of breast cancer involved miRNAs in MDA-MB-231 cell line. Clin Nutr ESPEN, 46:477-483.
5. Dai J, Shen J, Pan W, Shen S, et al (2013). Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro. Lipids Health Dis, 12:71.
6. Liu JR, Li BX, Chen BQ, et al (2002). Effect of cis-9, trans-11-conjugated linoleic acid on cell cycle of gastric adenocarcinoma cell line (SGC-7901). World J Gastroenterol, 8 (2):224-9.
7. Elahirad S, Elieh Ali Komi D, Kiani A, et al (2022). Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Polymorphisms, Their Serum Levels, and Activities with Coronary Artery Calcification (CAC) in an Iranian Population. Cardiovasc Toxicol, 22 (2):118-129.
8. Najafi K, Komi DEA, Khazaie H, et al (2018). Investigation of Serum Levels and Activity of Matrix Metalloproteinases 2 and 9 (MMP2, 9) in Opioid and Methamphetamine-Dependent Patients. Acta Med Iran, 56 (9):559-562.
9. Xie YL, Tao WH, Yang TX, et al (2016). Anticancer effect of cucurbitacin B on MKN-45 cells via inhibition of the JAK2/STAT3 signaling pathway. Exp Ther Med, 12 (4):2709-2715.
10. Yokozaki H (2000). Molecular characteristics of eight gastric cancer cell lines established in Japan. Pathol Int, 50 (10):767-77.
11. Soe ZY, Prajuabjinda O, Myint PK, et al (2019). Talin-2 regulates integrin functions in exosomes. Biochem Biophys Res Commun, 512 (3):429-434.
12. Mostmans Y, De Smedt K, Richert B, et al (2021). Markers for the involvement of endothelial cells and the coagulation system in chronic urticaria: A systematic review. Allergy, 76 (10):2998-3016.
13. Elieh Ali Komi D, Wöhrl S, Bielory L (2020). Mast Cell Biology at Molecular Level: a Comprehensive Review. Clin Rev Allergy Immunol, 58 (3):342-365.
14. Komi DEA, Redegeld FA (2020). Role of Mast Cells in Shaping the Tumor Microenvironment. Clin Rev Allergy Immunol, 58 (3):313-325.
15. Elieh Ali Komi D, Kuebler WM (2022). Significance of Mast Cell Formed Extracellular Traps in Microbial Defense. Clin Rev Allergy Immunol, 62(1):160-179.
16. Komi DEA, Khomtchouk K, Santa Maria PL (2020). A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms. Clin Rev Allergy Immunol, 58 (3):298-312.
17. Liu HN, Wu H, Tseng YJ, et al (2018). Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer. BMC Cancer, 18 (1):415.
18. Feng Q, Wu X, Li F, et al (2017). miR-27b inhibits gastric cancer metastasis by targeting NR2F2. Protein Cell, 8 (2):114-122.
19. Wang H, Wang G, Tian WL (2019). [MiR-126 inhibits the proliferation and invasion of gastric cancer by downregulation of IGF-1R]. Zhonghua Zhong Liu Za Zhi, 41 (7):508-515.
20. Feng R, Sah BK, Beeharry MK, et al (2018). Dysregulation of miR-126/Crk protein axis predicts poor prognosis in gastric cancer patients. Cancer Biomark, 21 (2):335-343.
21. Wang J, Jiao Y, Cui L, Jiang L (2017). miR-30 functions as an oncomiR in gastric cancer cells through regulation of P53-mediated mitochondrial apoptotic pathway. Biosci Biotechnol Biochem, 81 (1):119-126.
22. Peng Y, Zhang X, Lin H, et al (2018). Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer. Oncol Rep, 40 (6):3323-3334.
23. Bao J, Zou JH, Li CY, Zheng GQ (2016). miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B. Eur Rev Med Pharmacol Sci, 20 (21):4487-4493.
24. Yoshida K, Kodera Y, Kochi M, et al (2019). Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol, 37 (15):1296-1304.
25. Yamada Y, Boku N, Mizusawa J, et al (2019). Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol, 4 (7):501-510.
26. Mirabdaly S, Elieh Ali Komi D, Shakiba Y,et al(2020). Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF, anti-proliferatory cytotoxic and apoptotic properties. Mol Biol Rep, 47 (2):1187-1197.
27. Shekari N, Asghari F, Haghnavaz N, et al (2019). Let-7a Could Serve as A Biomarker for Chemo-Responsiveness to Docetaxel in Gastric Cancer. Anticancer Agents Med Chem, 19 (3):304-309.
28. Sasaki T, Fujii K, Yoshida K, et al (2006). Peritoneal metastasis inhibition by linoleic acid with activation of PPARgamma in human gastrointestinal cancer cells. Virchows Arch, 448 (4):422-7.
29. Chen BQ, Xue YB, Liu JR, et al (2003). Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms. World J Gastroenterol, 9 (1):44-9.
30. Ohmori H, Sasahira T, Fujii K, Yi L, et al (2008). Linoleic-acid-induced growth suppression induces quiescent cancer cell nests in nude mice. Pathobiology, 75 (4):226-32.
31. Connolly JM, Liu XH, Rose DP (1996). Dietary linoleic acid-stimulated human breast cancer cell growth and metastasis in nude mice and their suppression by indomethacin, a cyclooxygenase inhibitor. Nutr Cancer, 25 (3):231-40.
32. Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, et al (2011). Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A. Int J Biochem Cell Biol, 43 (12):1782-91.
33. Yang Y, Chen B, Xue Y, Zheng Y (2003). [Effects of c9, t11-conjugated linoleic acid on the metastasis of human gastric carcinoma cell line]. Wei Sheng Yan Jiu, 32 (2):117-9.
34. Kwon JI, Kim GY, Park KY, et al (2008). Induction of apoptosis by linoleic acid is associated with the modulation of Bcl-2 family and Fas/FasL system and activation of caspases in AGS human gastric adenocarcinoma cells. J Med Food, 11 (1):1-8.
35. Choi YH (2014). Linoleic Acid-Induced Growth Inhibition of Human Gastric Epithelial Adenocarcinoma AGS Cells is Associated with Down-Regulation of Prostaglandin E2 Synthesis and Telomerase Activity. J Cancer Prev, 19 (1):31-8.
36. Puebla C, Cisterna BA, Salas DP, et al (2016). Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism. Biochim Biophys Acta, 1861 (5):439-48.
37. Kuniyasu H, Yoshida K, Sasaki T, et al (2006). Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells. Int J Cancer, 118 (3):571-6.
38. Nishioka N, Matsuoka T, Yashiro M, et al (2011). Linoleic acid enhances angiogenesis through suppression of angiostatin induced by plasminogen activator inhibitor 1. Br J Cancer, 105 (11):1750-8.
39. Matsuoka T, Adair JE, Lih FB, et al (2010). Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice. Br J Cancer, 103 (8):1182-91.
40. Haghnavaz N, Asghari F, Elieh Ali Komi D, et al (2018). HER2 positivity may confer resistance to therapy with paclitaxel in breast cancer cell lines. Artif Cells Nanomed Biotechnol, 46 (3):518-523.
41. Alipoor SD, Chang H (2023). Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma. Cells, 12 (7):1030.
42. Parra P, Serra F, Palou A (2010). Expression of adipose microRNAs is sensitive to dietary conjugated linoleic acid treatment in mice. PLoS One, 5 (9):e13005.
43. Feng R, Beeharry MK, Lu S, et al (2018). Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer. Cancer Biomark, 22 (1):119-126.
44. Li Q, Wang G, Wang H (2018). MiR-126 functions as a tumor suppressor by targeting SRPK1 in human gastric cancer. Oncol Res, 26(9):1345-1353.
| Files | ||
| Issue | Vol 53 No 7 (2024) | |
| Section | Original Article(s) | |
| Keywords | ||
| Gastric cancer Linoleic acid Talin-2 | ||
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How to Cite
1.
Elieh-Ali-Komi D, Kazemi T, Shekari N, Farzamifar P, Eghbali E, Mansoori B, Baradaran B, Shirmohamadi M. Linoleic Acid Modulates the Expression of Metastatic and Angiogenic Markers MMP-2 and Talin-2 in Gastric Cancer Cell Line MKN-45. Iran J Public Health. 2024;53(7):1612-1620.
