نقش miR-182 و ژن FOXO در بیماران مبتلا به سرطان کولورکتال
محورهای موضوعی :
ژنتیک
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)
تاریخ دریافت : 1401/01/04
تاریخ پذیرش : 1401/03/17
تاریخ انتشار : 1401/04/01
کلید واژه:
FOXO,
سرطان کولورکتال,
miR-182,
چکیده مقاله :
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.
چکیده انگلیسی:
Objective: Colorectal cancer (CRC) is the third most common cancer in the world. Every year, more than 2-1 million new patients with this cancer are diagnosed and more than 600,000 people die. In the past decade, it has been established that aberrant changes in microRNA expression play a functional role in the initiation and progression of CRC. The aim of this study is to investigate the role of miR-182 and its effect on the regulation of FOXO proteins, especially in the initiation and progression of tumors in patients with CRC.Materials and methods: In this research, recent articles and reports from the Cancer Genome Atlas (TCGA) database regarding miR-182, as an oncogene that negatively regulates several tumor suppressor genes, including BRCA1, FOXO1, FOXO3, and MITF, were analyzed and checked.Findings: The results show that miR-182 is significantly increased in CRC tissue compared to normal intestinal tissue and causes negative regulation of FOXO1 and FOXO3 genes.Conclusion: The regulation of FOXO proteins by miR-182 is involved in tumor initiation and progression in CRC patients. How signaling networks integrate with FOXO transcription factors to modulate developmental, metabolic, and tumor suppressor functions in normal tissues and colorectal cancer provides a new perspective on tumorigenesis and metastasis.
منابع و مأخذ:
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.
_||_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.
