نقش miR-182 و ژن FOXO در بیماران مبتلا به سرطان کولورکتال
الموضوعات :
مژگان سقازاده
1
(استادیار، گروه میکروبیولوژی، واحد قم، دانشگاه آزاد اسلامی، قم، ایران)
عفت سیدهاشمی
2
(دانشجوی دکتری، گروه پزشکی مولکولی، پژوهشکده بیوتکنولوژی پزشکی، پژوهشگاه ملی مهندسی ژنتیک و زیست فناوری، تهران، ایران.)
ماسیمو نگرینی
3
(استاد، گروه تشخیص و مورفولوژی، دانشکده پزشکی، دانشگاه فرارا، فرارا، ایتالیا.)
شهلا محمدگنجی
4
(استادیار، گروه پزشکی مولکولی، پژوهشکده بیوتکنولوژی پزشکی، پژوهشگاه ملی مهندسی ژنتیک و زیست فناوری، تهران، ایران)
تاريخ الإرسال : 21 الخميس , شعبان, 1443
تاريخ التأكيد : 08 الثلاثاء , ذو القعدة, 1443
تاريخ الإصدار : 23 الأربعاء , ذو القعدة, 1443
الکلمات المفتاحية:
FOXO,
سرطان کولورکتال,
miR-182,
ملخص المقالة :
هدف: سرطان کولورکتال (CRC) سومین سرطان شایع در دنیا است. سالانه بیش از 1-2 میلیون بیمار جدید مبتلا به این سرطان شناسایی و بیش از600.000 نفر مبتلایان فوت می‌کنند. در دهه گذشته، مشخص شده که تغییرات نابجا در بیان microRNA نقشی کاربردی در شروع و پیشرفت CRC دارد. هدف پژوهش حاضر، بررسی نقش miR-182 و اثر آن بر تنظیم پروتئین‌های FOXO بخصوص در شروع و پیشرفت تومور در بیماران مبتلا به CRC است.مواد و روش‌ها: در این پژوهش مقالات اخیر و گزارش‌های پایگاه داده (TCGA) اطلس ژنوم سرطان در خصوص miR-182، به عنوان انکوژنی که باعث تنظیم منفی چندین ژن سرکوبگر تومور از جمله BRCA1، FOXO1، FOXO3و MITF می‌شود، مورد تحلیل و بررسی قرار گرفته است.یافته‌ها: نتایج نشان می‌دهد که miR-182 به طور قابل توجهی در بافت CRC در مقایسه با بافت طبیعی روده افزایش بیان دارد و باعث تنظیم منفی ژن‌های FOXO1و FOXO3 می‌شود.نتیجه‌گیری: تنظیم پروتئین‌های FOXO توسط miR-182 در شروع و پیشرفت تومور در بیماران مبتلا به CRC نقش دارد. نحوه ادغام شبکه‌های سیگنالینگ با فاکتورهای رونویسی FOXO برای تعدیل عملکردهای رشدی، متابولیک و سرکوب‌کننده تومور در بافت‌های طبیعی و سرطان کولورکتال دیدگاه جدیدی در مورد تومورزایی و متاستاز ارائه می‌دهد.
المصادر:
Gonzalez-Pons M & Cruz-Correa M. Colorectal cancer biomarkers: where are we now? Biomed Res Int. 2015; 2015: 1–14.
PICARD, E. & et al. Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer. Frontiers in Immunology. 2020; 11: 369.
Laissue, P. The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis. Molecular cancer. 2019; 18(1): 1-13.
4. Fabian MR, Sonenberg N & Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annual review of biochemistry. 2010; 79: 351-79.
5. Bartel DP. MicroRNAs: target recognition and regulatory functions. 2009; 136(2): 215-33.
6. Bernardo BC, Charchar FJ, Lin RC & McMullen JR. A microRNA guide for clinicians and basic scientists: background and experimental techniques. Heart, Lung and Circulation. 2012; 21(3): 131-42.
7. Mazeh, Haggi & et al. The diagnostic and prognostic role of microRNA in colorectal cancer-a comprehensive review. Journal of cancer.3 (2013): 281.
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9. Hamfjord J, Stangeland AM, Hughes T, Skrede ML, Tveit KM, Ikdahl T & et al. Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing. PloS one. 2012; 7(4): e34150.
Nishida N, Nagahara M, Sato T, Mimori K, Sudo T, Tanaka F & et al. Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. Clinical Cancer Research. 2012; 18(11): 3054–3070.
DOI: https://doi.org/10.1158/1078-0432.CCR-11-1078
Cekaite, L. & et al. MiR-9,-31, and-182 deregulation promote proliferation and tumor cell survival in colon cancer. Neoplasia. 2012, 14.9: 868-IN21.
12. WEI Q & LEI R. Roles of miR‐182 in sensory organ development and cancer. Thoracic cancer. 2015; 6.1: 2-9.
13. Zhang, YU & et al. miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer. Oncology reports. 2015; 33.5: 2592-2598.
14. Jiramongkol, Y. & Eric W-F. FOXO transcription factor family in cancer and metastasis. Cancer and Metastasis Reviews. 2020; 39.3: 681-709.
Qi W, Weber CR, Wasland K & Savkovic SD. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor. FOXO3 activity. BMC Cancer. 2011; 11: 219.
DOI: 10.1186/1471-2407-11-219.
16. Ericson K, Gan C, Cheong I, Rago C, Samuels Y, Velculescu VE & et al. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proc Natl Acad Sci. 2010; 107: 2598–2603.
DOI:1073/pnas.0914018107
17. Tenbaum SP, Ordóñez-Morán P, Puig I, Chicote I, Arqués O, Landolfi S & et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med. 2012; 18: 892–901. DOI:1038/nm.2772
18. Shorning, BY & et al. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. International Journal of Molecular Sciences. 2020; 21.12: 4507.
19. Fernández de Mattos S, Villalonga P, Clardy J & Lam EW-F. FOXO3a mediates the cytotoxic effects of cisplatin in colon cancer cells. Mol Cancer Ther. 2008; 7: 3237–3246. DOI:1158/1535-7163.MCT-08-0398.
20. Germani A, Matrone A, Grossi V, Peserico A, Sanese P, Liuzzi M & et al. Targeted therapy against chemoresistant colorectal cancers: inhibition of p38α modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FOXO Cancer Lett. 2014; 344: 110–118. DOI: 10.1016/j.canlet.2013.10.035.
21. Gao F & Wang W. MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO Mol Med Rep. 2015; 11: 1200–1206.
DOI: 10.3892/mmr.2014.2854.
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24. Zhang J, Zhang K, Zhou L, Wu W, Jiang T, Cao J & et al. Expression and potential correlation among Forkhead box protein M1, Caveolin-1 and E-cadherin in colorectal cancer. Oncol Lett. 2016; 12: 2381–2388. DOI:3892/ol.2016.4915.
25. Weng W, Okugawa Y, Toden S, Toiyama Y, Kusunoki M & Goel A. FOXM1 and FOXQ1 are promising prognostic biomarkers and novel targets of tumor-suppressive miR-342 in human colorectal cancer. Clin Cancer Res. 2016; 22: 4947–4957.
DOI:1158/1078-0432.CCR-16-0360.
26. Dai Y, Wang M, Wu H, Xiao M, Liu H & Zhang D. Loss of FOXN3 in colon cancer activates beta-catenin/TCF signaling and promotes the growth and migration of cancer cells. Oncotarget. 2017; 8: 9783-93.
27. Marzi L, Combes E, Vié N, Ayrolles-Torro A, Tosi D, Desigaud D & et al. FOXO3a and the MAPK p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer. Br J Cancer. 2016; 115: 1223–1233. DOI:1038/bjc.2016.313.
28. Jiramongkol Y, LAM, Eric W.-F. FOXO transcription factor family in cancer and metastasis. Cancer and Metastasis Reviews. 2020; 39: 681-709.
29. Garcia-Alonso, L & et al. Benchmark and integration of resources for the estimation of human transcription factor activities. Genome research. 2019; 29.8: 1363-1375.
30. Eric W.-F. & et al. Forkhead box proteins: tuning forks for transcriptional harmony. Nature Reviews Cancer. 2013; 13.7: 482-495.
31. Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA & et al. The transcription factor encyclopedia. Genome Biol. 2012; 13: R24.
DOI:1186/gb-2012-13-3-r24.
32. LIU, J & et al. The Biogenesis of miRNAs and Their Role in the Development of Amyotrophic Lateral Sclerosis. Cells. 2022; 11.3: 572.
33. Urbánek P & Klotz L‐O. Posttranscriptional regulation of FOXO expression: microRNAs and beyond. British journal of pharmacology. 2017; 174.12 (2017): 1514-1532.
_||_Gonzalez-Pons M & Cruz-Correa M. Colorectal cancer biomarkers: where are we now? Biomed Res Int. 2015; 2015: 1–14.
PICARD, E. & et al. Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer. Frontiers in Immunology. 2020; 11: 369.
Laissue, P. The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis. Molecular cancer. 2019; 18(1): 1-13.
4. Fabian MR, Sonenberg N & Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annual review of biochemistry. 2010; 79: 351-79.
5. Bartel DP. MicroRNAs: target recognition and regulatory functions. 2009; 136(2): 215-33.
6. Bernardo BC, Charchar FJ, Lin RC & McMullen JR. A microRNA guide for clinicians and basic scientists: background and experimental techniques. Heart, Lung and Circulation. 2012; 21(3): 131-42.
7. Mazeh, Haggi & et al. The diagnostic and prognostic role of microRNA in colorectal cancer-a comprehensive review. Journal of cancer.3 (2013): 281.
8. Ma Y, Li W & Wang H. Roles of miRNA in the initiation and development of colorectal carcinoma. Current pharmaceutical design. 2013; 19(7): 1253-61.
9. Hamfjord J, Stangeland AM, Hughes T, Skrede ML, Tveit KM, Ikdahl T & et al. Differential expression of miRNAs in colorectal cancer: comparison of paired tumor tissue and adjacent normal mucosa using high-throughput sequencing. PloS one. 2012; 7(4): e34150.
Nishida N, Nagahara M, Sato T, Mimori K, Sudo T, Tanaka F & et al. Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. Clinical Cancer Research. 2012; 18(11): 3054–3070.
DOI: https://doi.org/10.1158/1078-0432.CCR-11-1078
Cekaite, L. & et al. MiR-9,-31, and-182 deregulation promote proliferation and tumor cell survival in colon cancer. Neoplasia. 2012, 14.9: 868-IN21.
12. WEI Q & LEI R. Roles of miR‐182 in sensory organ development and cancer. Thoracic cancer. 2015; 6.1: 2-9.
13. Zhang, YU & et al. miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer. Oncology reports. 2015; 33.5: 2592-2598.
14. Jiramongkol, Y. & Eric W-F. FOXO transcription factor family in cancer and metastasis. Cancer and Metastasis Reviews. 2020; 39.3: 681-709.
Qi W, Weber CR, Wasland K & Savkovic SD. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor. FOXO3 activity. BMC Cancer. 2011; 11: 219.
DOI: 10.1186/1471-2407-11-219.
16. Ericson K, Gan C, Cheong I, Rago C, Samuels Y, Velculescu VE & et al. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proc Natl Acad Sci. 2010; 107: 2598–2603.
DOI:1073/pnas.0914018107
17. Tenbaum SP, Ordóñez-Morán P, Puig I, Chicote I, Arqués O, Landolfi S & et al. β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer. Nat Med. 2012; 18: 892–901. DOI:1038/nm.2772
18. Shorning, BY & et al. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. International Journal of Molecular Sciences. 2020; 21.12: 4507.
19. Fernández de Mattos S, Villalonga P, Clardy J & Lam EW-F. FOXO3a mediates the cytotoxic effects of cisplatin in colon cancer cells. Mol Cancer Ther. 2008; 7: 3237–3246. DOI:1158/1535-7163.MCT-08-0398.
20. Germani A, Matrone A, Grossi V, Peserico A, Sanese P, Liuzzi M & et al. Targeted therapy against chemoresistant colorectal cancers: inhibition of p38α modulates the effect of cisplatin in vitro and in vivo through the tumor suppressor FOXO Cancer Lett. 2014; 344: 110–118. DOI: 10.1016/j.canlet.2013.10.035.
21. Gao F & Wang W. MicroRNA-96 promotes the proliferation of colorectal cancer cells and targets tumor protein p53 inducible nuclear protein 1, forkhead box protein O1 (FOXO1) and FOXO Mol Med Rep. 2015; 11: 1200–1206.
DOI: 10.3892/mmr.2014.2854.
22. Hornsveld M, Dansen TB, Derksen PW & Burgering BMT. Re-evaluating the role of FOXOs in cancer. Semin Cancer Biol. 2018; 50: 90–100.
DOI:1016/j.semcancer.2017.11.017.
23. Koo C-Y, Muir KW & Lam EW-F. FOXM1: from cancer initiation to progression and treatment. Biochim Biophys Acta. 1819; 2012: 28–37.
24. Zhang J, Zhang K, Zhou L, Wu W, Jiang T, Cao J & et al. Expression and potential correlation among Forkhead box protein M1, Caveolin-1 and E-cadherin in colorectal cancer. Oncol Lett. 2016; 12: 2381–2388. DOI:3892/ol.2016.4915.
25. Weng W, Okugawa Y, Toden S, Toiyama Y, Kusunoki M & Goel A. FOXM1 and FOXQ1 are promising prognostic biomarkers and novel targets of tumor-suppressive miR-342 in human colorectal cancer. Clin Cancer Res. 2016; 22: 4947–4957.
DOI:1158/1078-0432.CCR-16-0360.
26. Dai Y, Wang M, Wu H, Xiao M, Liu H & Zhang D. Loss of FOXN3 in colon cancer activates beta-catenin/TCF signaling and promotes the growth and migration of cancer cells. Oncotarget. 2017; 8: 9783-93.
27. Marzi L, Combes E, Vié N, Ayrolles-Torro A, Tosi D, Desigaud D & et al. FOXO3a and the MAPK p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer. Br J Cancer. 2016; 115: 1223–1233. DOI:1038/bjc.2016.313.
28. Jiramongkol Y, LAM, Eric W.-F. FOXO transcription factor family in cancer and metastasis. Cancer and Metastasis Reviews. 2020; 39: 681-709.
29. Garcia-Alonso, L & et al. Benchmark and integration of resources for the estimation of human transcription factor activities. Genome research. 2019; 29.8: 1363-1375.
30. Eric W.-F. & et al. Forkhead box proteins: tuning forks for transcriptional harmony. Nature Reviews Cancer. 2013; 13.7: 482-495.
31. Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA & et al. The transcription factor encyclopedia. Genome Biol. 2012; 13: R24.
DOI:1186/gb-2012-13-3-r24.
32. LIU, J & et al. The Biogenesis of miRNAs and Their Role in the Development of Amyotrophic Lateral Sclerosis. Cells. 2022; 11.3: 572.
33. Urbánek P & Klotz L‐O. Posttranscriptional regulation of FOXO expression: microRNAs and beyond. British journal of pharmacology. 2017; 174.12 (2017): 1514-1532.
