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Investigating the Expression Level of CCAT2 and BIM Genes in Colorectal Cancer Patients | ||
| Journal of Genetic Resources | ||
| دوره 11، شماره 1، 2025، صفحه 31-40 اصل مقاله (459.74 K) | ||
| نوع مقاله: Research Article | ||
| شناسه دیجیتال (DOI): 10.22080/jgr.2025.26131.1399 | ||
| نویسندگان | ||
| Alireza Rangin* ؛ Fatemeh Jenagh | ||
| Department of Biology, Ilam Branch, Islamic Azad University, Ilam, Iran | ||
| تاریخ دریافت: 20 مرداد 1403، تاریخ بازنگری: 03 بهمن 1403، تاریخ پذیرش: 04 مهر 1403 | ||
| چکیده | ||
| Colon cancer ranks as the second most common cancer among women and the third among men globally. Research has demonstrated that reduced expression of the Bcl-2-like protein 11 (BIM) gene in various cancers, including colon cancer, lowers cancer cell apoptosis, thereby enhancing their survival. Another crucial molecular factor in cancer is non-coding RNAs, which influence protein-coding genes such as oncogenes and tumor suppressor genes. Colon cancer-associated transcript 2 (CCAT2), a long non-coding RNA, is known to play a regulatory role in several cancers, affecting gene expression. This study aimed to measure and compare the expression levels of BIM and CCAT2 genes in colon cancer tissues and healthy tissues. Total RNA was extracted from paraffin-embedded tissue samples using the Trizol method. Specific primers for the BIM and CCAT2 genes, along with the Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) reference gene, were designed using Oligo 7 software. Following cDNA synthesis, RT-PCR was conducted to assess gene expression levels relative to the GAPDH control gene. Data analysis, performed using GraphPad Prism and Excel2020 with One Way ANOVA and one-sided T-test, revealed a 10-fold decrease in BIM gene expression in cancerous tissues compared to healthy tissues (P < 0.01). In contrast, CCAT2 gene expression was 325 times higher in cancerous tissues (P < 0.0001). The present study revealed that the expression of the CCAT2 gene was significantly elevated in colon cancer patients compared to healthy individuals. This increase may be mediated through various signaling pathways, including BOP1, mTOR, and Wnt. Additionally, interactions with other regulatory factors, such as miRNAs, can contribute to tumor cell proliferation, inhibition of apoptosis, and metastasis in patients. The reduced BIM expression could result from genetic and epigenetic mutations disrupting the AKT and ERK pathways, thereby promoting tumor growth. | ||
| کلیدواژه‌ها | ||
| Apoptosis؛ BIM؛ CCAT2؛ LncRNA؛ Non-coding RNA | ||
| مراجع | ||
|
Aliperti, V., Skonieczna, J., & Cerase, A. (2021). Long non-coding RNA (lncRNA) roles in cell biology, neurodevelopment and neurological disorders. Non-coding RNA, 7(2), 36. https://doi.org/10.3390/ncrna7020036
Bahar, M. E., Kim, H. J., & Kim, D. R. (2023). Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies. Signal Transduction and Targeted Therapy, 8(1), 455. https://doi.org/10.1038/s41392-023-01705-z
Chakraborty, A. R., Robey, R. W., Luchenko, V. L., Zhan, Z., Piekarz, R. L., Gillet, J. P., Kossenkov, A. V., Wilkerson, J., Showe, L. C., Gottesman, M. M., Collie, N. L., & Bates, S. E. (2013). MAPK pathway activation leads to Bim loss and histone deacetylase inhibitor resistance: rationale to combine romidepsin with an MEK inhibitor. Blood, The Journal of the American Society of Hematology, 121(20), 4115-4125. https://doi.org/10.1182/blood-2012-08-449140
Cheng, Y., Yang, M., & Peng, J. (2019). Correlation the between the regulation of miRNA‑1 in c‑Met‑induced EMT and cervical cancer progression. Oncology Letters, 17(3), 3341-3349. https://doi.org/10.3892/ol.2019.9971
Delattre, J. F., Selcen Oguz Erdogan, A., Cohen, R., Shi, Q., Emile, J. F., Taieb, J., Tabernero, J., André, T., Meyerhardt, J. A., Nagtegaal, I. D., & Svrcek, M. (2022). A comprehensive overview of tumour deposits in colorectal cancer: Towards a next TNM classification. Cancer Treatment Reviews, 103, 102325. https://doi.org/10.1016/j.ctrv.2021.102325
Faber, A. C., Ebi, H., Costa, C., & Engelman, J. A. (2012). Chapter Sixteen - Apoptosis In Targeted Therapy Responses: The Role of BIM. In K. S. M. Smalley (Ed.), Advances in Pharmacology (Vol. 65, pp. 519-542). Academic Press. https://doi.org/10.1016/B978-0-12-397927-8.00016-6
Foßelteder, J., Calin, G., & Pichler, M. (2018). Long non-coding RNA CCAT2 as a therapeutic target in colorectal cancer. Expert Opinion on Therapeutic Targets, 22. https://doi.org/10.1080/14728222.2018.1541453
Greenhough, A., Wallam, C. A., Hicks, D. J., Moorghen, M., Williams, A. C., & Paraskeva, C. (2010). The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene, 29(23), 3398-3410. https://doi.org/10.1038/onc.2010.94
Grisanzio, C., & Freedman, M. (2010). Chromosome 8q24-associated cancers and MYC. Genes and Cancer, 1, 555-559. https://doi.org/10.1177/1947601910381380
Harada, H., & Grant, S. (2012). Targeting the regulatory machinery of BIM for cancer therapy. Eukaryotic Gene Expression, 22(2), 117-129. https://doi.org/10.1615/critreveukargeneexpr.v22.i2.40
Hata, A. N., Engelman, J. A., & Faber, A. C. (2015). The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discovery, 5(5), 475-487. https://doi.org/10.1158/2159-8290.Cd-15-0011
Huang, B., Yu, M., Guan, R., Liu, D., & Hou, B. (2020). A comprehensive exploration of the lncRNA CCAT2: A pan-cancer analysis based on 33 cancer types and 13285 cases. Disease Markers, 2020, 5354702. https://doi.org/10.1155/2020/5354702
Huang, S., Qing, C., Huang, Z., & Zhu, Y. (2016). The long non-coding RNA CCAT2 is up-regulated in ovarian cancer and associated with poor prognosis. Diagnostic Pathology, 11 (1), 49. https://doi.org/10.1186/s13000-016-0499-x
Javed, Z., Khan, K., Sadia, H., Raza, S., Salehi, B., Sharifi-Rad, J., & Cho, W. C. (2020). LncRNA & Wnt signaling in colorectal cancer. Cancer Cell International, 20(1), 326. https://doi.org/10.1186/s12935-020-01412-7
Kasagi, Y., Oki, E., Ando, K., Ito, S., Iguchi, T., Sugiyama, M., Nakashima, Y., Ohgaki, K., Saeki, H., & Mimori, K. (2017). The expression of CCAT2, a novel long noncoding RNA transcript, and rs6983267 single-nucleotide polymorphism genotypes in colorectal cancers. Oncology, 92(1), 48-54. https://doi.org/10.1159/000452143
Kim, H. J., Maiti, P., & Barrientos, A. (2017, December). Mitochondrial ribosomes in cancer. In Seminars in Cancer Biology, 47, 67-81. https://doi.org/10.1016/j.semcancer.2017.04.004
Ling, H., Spizzo, R., Atlasi, Y., Nicoloso, M., Shimizu, M., Redis, R. S., Nishida, N., Gafà, R., Song, J., & Guo, Z. (2013). CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Research, 23(9), 1446-1461. https://doi.org/10.1101/gr.152942.112
Liu, X.-Y., Zheng, C.-B., Wang, T., Xu, J., Zhang, M., Gou, L.-S., Jin, L., Qi, X., Zeng, X., & Li, H. (2020). SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer. Clinical Science, 134(2), 155-167. https://doi.org/10.1042/CS20190865
Mhaidat, N. M., Alzoubi, K. H., Al-Akhras, M. A., & Al-Bashir, N. M. (2019). Study of the epigenetic down-regulation of Bim on colorectal cancer chemotherapy response. Journal of King Saud University - Science, 31 (4), 1154-1159. https://doi.org/10.1016/j.jksus.2017.09.012
Moradi, F., Mohajerani, F., & Sadeghizadeh, M. (2022). CCAT2 knockdown inhibits cell growth, and migration and promotes apoptosis through regulating the hsa-mir-145-5p/AKT3/mTOR axis in tamoxifen-resistant MCF7 cells. Life Sciences, 311, 121183. https://doi.org/10.1016/j.lfs.2022.121183
Pirlog, R., Drula, R., Nutu, A.-M., Calin, G., & Berindan - Neagoe, I. (2021). The roles of the colon cancer associated transcript 2 (CCAT2) long non-coding RNA in cancer: a comprehensive characterization of the tumorigenic and molecular functions. International Journal of Molecular Sciences, 22, 12491. https://doi.org/10.3390/ijms222212491
Ramzi, N. H., Chahil, J. K., Lye, S. H., Munretnam, K., Sahadevappa, K. I., Velapasamy, S., Hashim, N. A., Cheah, S. K., Lim, G. C., Hussein, H., Haron, M. R., Alex, L., & Ler, L. W. (2014). Role of genetic and environment risk factors in the aetiology of colorectal cancer in Malaysia. Indian Journal of Medical Research, 140 (6), 873-882. http://dx.doi.org/10.13140/2.1.1836.8641
Rennoll, S., & Yochum, G. (2015). Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer. World Journal of Biological Chemistry, 6(4), 290-300. https://doi.org/10.4331/wjbc.v6.i4.290
Sanaei, M. J., Razi, S., Pourbagheri-Sigaroodi, A., & Bashash, D. (2022). The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles. Translational Oncology, 18, 101364. https://doi.org/10.1016/j.tranon.2022.101364
Shamas-Din, A., Kale, J., Leber, B., & Andrews, D. W. (2013). Mechanisms of action of Bcl-2 family proteins. Cold Spring Harbor Perspectives in Biology, 5(4), a008714. https://doi.org/10.1101/cshperspect.a008714
Sionov, R. V., Vlahopoulos, S. A., & Granot, Z. (2015). Regulation of Bim in health and disease. Oncotarget, 6(27), 23058-23134. https://doi.org/10.18632/oncotarget.5492
Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, R. C., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M. C., Donia, M., Fagone, P., Malaponte, G., Nicoletti, F., Libra, M., Milella, M., Tafuri, A., Bonati, A., Bäsecke, J., . . . McCubrey, J. A. (2011). Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging, 3(3), 192-222. https://doi.org/10.18632/aging.100296
Swier, L., Dzikiewicz-Krawczyk, A., Winkle, M., van den Berg, A., & Kluiver, J. (2019). Intricate crosstalk between MYC and non-coding RNAs regulates hallmarks of cancer. Molecular Oncology, 13(1), 26-45. https://doi.org/10.1002/1878-0261.12409
Tagscherer, K., Fassl, A., Sinkovic, T., Richter, J., Schecher, S., Macher-Goeppinger, S., & Roth, W. (2016). MicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen species. Cancer Cell International, 16 (1), 48. https://doi.org/10.1186/s12935-016-0321-6
Wang, D., Chen, Z., Xu, H., He, A., Liu, Y., & Huang, W. (2017). Long noncoding RNA CCAT2 as a novel biomaker of metastasis and prognosis in human cancer: a meta-analysis. Oncotarget, 8(43), 75664-75674. https://doi.org/10.18632/oncotarget.18161
Wang, J., Tian, Y., Zheng, H., Ding, Y., & Wang, X. (2019). An integrated analysis reveals the oncogenic function of lncRNA LINC00511 in human ovarian cancer. Cancer Medicine, 8 (6), 3026–3035. https://doi.org/10.1002/cam4.2151
Wang, K. C., & Chang, H. Y. (2011). Molecular mechanisms of long noncoding RNAs. Molecular Cell, 43(6), 904-914. https://doi.org/10.1016/j.molcel.2011.08.018
Wang, L., Duan, W., Yan, S., Xie, Y., & Wang, C. (2019). Circulating long non-coding RNA colon cancer-associated transcript 2 protected by exosome as a potential biomarker for colorectal cancer. Biomedicine & Pharmacotherapy, 113, 108758. https://doi.org/10.1016/j.biopha.2019.108758
Warren, C. F. A., Wong-Brown, M. W., & Bowden, N. A. (2019). BCL-2 family isoforms in apoptosis and cancer. Cell Death and Disease, 10(3), 177. https://doi.org/10.1038/s41419-019-1407-6
Wu L, Jin L, Zhang W, Zhang L. Roles of Long Non-Coding RNA CCAT2 in Cervical Cancer Cell Growth and Apoptosis. Med Sci Monit. 2016 Mar 17;22:875-9. doi: 10.12659/msm.897754. PMID: 26983975; PMCID: PMC4801156. https://doi:10.12659/MSM.897754
Xin, Y., Li, Z., Zheng, H., Chan, M. T. V., & Wu, W. K. K. (2017). CCAT2: A novel oncogenic long non-coding RNA in human cancers. Cell Proliferation, 50 (3), e12342. https://doi.org/10.1111/cpr.12342
Yao, N., Yu, L., Zhu, B., Gan, H.-Y., & Guo, B.-Q. (2018). LncRNA GIHCG promotes development of ovarian cancer by regulating microRNA-429. European Review for Medical and Pharmacological Sciences, 22 (23), 7951-7960. https://doi.org/10.26355/eurrev_201812_16529
Zaki, A., Fawzy, A., Akel, S. Y., Gamal, H., & Elshimy, R. A. (2022). Evaluation of microRNA 92a expression and its target protein bim in Colorectal Cancer. Asian Pacific Journal of Cancer Prevention, 23(2), 723. https://doi.org/10.31557/APJCP.2022.23.2.723
Zeng, J., Du, T., Song, Y., Gao, Y., Li, F., Wu, R., Chen, Y., Li, W., Zhou, H., Yang, Y., & Pei, Z. (2017). Knockdown of long noncoding RNA CCAT2 inhibits cellular proliferation, invasion, and epithelial-mesenchymal transition in glioma cells. Oncology Research, 25 (6), 913-921. https://doi.org/10.3727/096504016X14792098307036
Zeng, X. Y., Jiang, X. Y., Yong, J. H., Xie, H., Yuan, J., Zeng, D., Dou, Y. Y., & Xiao, S. S. (2019). lncRNA ABHD11‐AS1, regulated by the EGFR pathway, contributes to the ovarian cancer tumorigenesis by epigenetically suppressing TIMP2. Cancer Medicine, 8 (16), 7074-7085. https://doi.org/10.1002/cam4.2538
Zhang, E., Han, L., Yin, D., He, X., Hong, L., Si, X., ... & Chen, J. (2017). H3K27 acetylation activated-long non-coding RNA CCAT1 affects cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous cell carcinoma. Nucleic Acids Research, 45(6), 3086-3101. https://doi.org/10.1093/nar/gkw1247
Zhao, H., Ming, T., Tang, S., Ren, S., Yang, H., Liu, M., Tao, Q., & Xu, H. (2022). Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Molecular Cancer, 21(1), 144. https://doi.org/10.1186/s12943-022-01616-7
Zhu, Y., & Li, X. (2023). Advances of Wnt signalling pathway in colorectal cancer. Cells, 12 (3), 447. https://doi.org/10.3390/cells12030447 | ||
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