Elucidating the Molecular Pathways of Long Noncoding RNA C6orf223 in Colorectal Cancer via microRNA Interactions and Transcriptomic Profiling
-
Sara Tutunchi
,
Amir-Reza Javanmard
,
Ghodratollah Panahi
,
Bahram M. Soltan
,
Atieh Akbari
,
Sayyed Mohammad Hossein Ghaderian
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with high-risk cases showing increased aggressiveness and poor prognosis. Recent studies suggest that long noncoding RNAs (lncRNAs) such as C6orf223 may play crucial roles in CRC progression. This study investigated the expression and regulatory role of C6orf223 in high-risk versus low-risk CRC patients, focusing on its potential as a biomarker for diagnosis and prognosis.
We conducted differential expression analysis using RNA-seq data to identify key genes in high-risk CRC, followed by correlation and pathway enrichment analyses to understand C6orf223. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves assessed the prognostic and diagnostic potential of C6orf223. RNA methylation and mutation patterns were analyzed to explore post-transcriptional regulation and genetic alterations in high-risk CRC.
C6orf223 was significantly upregulated in high-risk CRC. High C6orf223 expression was associated with poor overall survival, and a biomarker panel that includes C6orf223 and microRNAs showed strong potential for accurate diagnosis. Methylation and mutation analyses revealed potential mechanisms enhancing C6orf223’s stability and oncogenic activity.
Our findings indicate that C6orf223 acts as a binder to and inhibits tumor-suppressive microRNAs, reducing their availability to regulate cancer-promoting genes and may serve as a valuable biomarker for CRC diagnosis and prognosis. Further research on lncRNA-microRNA interactions could provide insights for novel CRC therapies.
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35. He J, Wu F, Han Z, Hu M, Lin W, Li Y, et al. Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of colorectal cancer—from the body fluid to tissue level. Front Oncol. 2021;11:632834.
36. Pan K, Xie Y. LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca2+-FAK signal pathway. Cell Death Dis. 2020;11(6):434.
2. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA. 2021;325(7):669–85.
3. Lewandowska A, Rudzki G, Lewandowski T, Stryjkowska-Gora A, Rudzki S. Risk factors for the diagnosis of colorectal cancer. Cancer Control. 2022;29:10732748211056692.
4. Alzahrani SM, Al Doghaither HA, Al-Ghafari AB. General insight into cancer: An overview of colorectal cancer. Mol Clin Oncol. 2021;15(6):271.
5. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021;14(10):101174.
6. Ghafouri-Fard S, Hussen BM, Gharebaghi A, Eghtedarian R, Taheri M. LncRNA signature in colorectal cancer. Pathol Pract. 2021;222:153432.
7. O’Brien SJ, Bishop C, Hallion J, Fiechter C, Scheurlen K, Paas M, et al. Long non-coding RNA (lncRNA) and epithelial-mesenchymal transition (EMT) in colorectal cancer: a systematic review. Cancer Biol Ther. 2020;21(9):769–81.
8. Liu Z, Guo C, Dang Q, Wang L, Liu L, Weng S, et al. Integrative analysis from multi-center studies identities a consensus machine learning-derived lncRNA signature for stage II/III colorectal cancer. EBioMedicine. 2022;75.
9. Ma YN, Hong YG, Yu GY, Jiang S yuan, Zhao B lun, Guo A, et al. LncRNA LBX2-AS1 promotes colorectal cancer progression and 5-fluorouracil resistance. Cancer Cell Int. 2021;21:1–13.
10. Bai H, Yan DS, Chen YL, Li QZ, Qi YC. Potential biomarkers: The hypomethylation of cg18949415 and cg22193385 sites in colon adenocarcinoma. Comput Biol Med. 2024;169:107884.
11. Zhang Y, Li L, Chu F, Zhang L, Zhang L, Wu H, et al. The tumor microenvironment in gastrointestinal adenocarcinomas revealed a prognostic and immunotherapeutic biomarker. Aging (Albany NY). 2022;14(24):10171.
12. Zhou Z, Tan F, Pei Q, Li C, Zhou Y, Li Y, et al. lncRNA SNHG4 modulates colorectal cancer cell cycle and cell proliferation through regulating miR-590-3p/CDK1 axis. Aging (Albany NY). 2021;13(7):9838.
13. Shariatmadar Taleghani A, Zohrab Beigi Y, Zare-Mirakabad F, Masoudi-Nejad A. Exploring ceRNA networks for key biomarkers in breast cancer subtypes and immune regulation. Sci Rep. 2023;13(1):20795.
14. Xu WW, Jin J, Wu X yu, Ren QL, Farzaneh M. MALAT1-related signaling pathways in colorectal cancer. Cancer Cell Int. 2022;22(1):126.
15. Uthman YA, Ibrahim KG, Abubakar B, Bello MB, Malami I, Imam MU, et al. MALAT1: a promising therapeutic target for the treatment of metastatic colorectal cancer. Biochem Pharmacol. 2021;190:114657.
16. Paszkowska A, Kolenda T, Guglas K, Kozłowska-Masłoń J, Podralska M, Teresiak A, et al. C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck Cancers. J Pers Med. 2022;12(10):1696.
17. Chen D, Dou C, Liu H, Xu B, Hu B, Kuang L, et al. Comprehensive analysis: Necroptosis-related lncRNAs can effectively predict the prognosis of glioma patients. Front Oncol. 2022;12:929233.
18. Nomiri S, Hoshyar R, Chamani E, Rezaei Z, Salmani F, Larki P, et al. Prediction and validation of GUCA2B as the hub-gene in colorectal cancer based on co-expression network analysis: In-silico and in-vivo study. Biomed Pharmacother. 2022;147:112691.
19. Zhong X, He X, Wang Y, Hu Z, Yu D, Huang H, et al. A Hypoxia-Related lncRNA Signature Correlates with Survival and Tumor Microenvironment in Colorectal Cancer. J Immunol Res. 2022;2022(1):9935705.
20. Pan K, Xie Y. LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca2+-FAK signal pathway. Cell Death Dis. 2020;11(6):434.
21. Zhou H, Xiong Y, Peng L, Wang R, Zhang H, Fu Z. LncRNA-cCSC1 modulates cancer stem cell properties in colorectal cancer via activation of the Hedgehog signaling pathway. J Cell Biochem. 2020;121(3):2510–24.
22. Chu Y, Liu Z, Liu J, Yu L, Zhang D, Pei F. Characterization of lncRNA-perturbed TLR-signaling network identifies novel lncRNA prognostic biomarkers in colorectal cancer. Front Cell Dev Biol. 2020;8:503.
23. Dastmalchi N, Safaralizadeh R, Nargesi MM. LncRNAs: potential novel prognostic and diagnostic biomarkers in colorectal cancer. Curr Med Chem. 2020;27(30):5067–77.
24. He J, Wu F, Han Z, Hu M, Lin W, Li Y, et al. Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of colorectal cancer--from the body fluid to tissue level. Front Oncol. 2021;11(3):632834.
25. Lu C, Luo X, Xing C, Mao Y, Xu Y, Gao W, et al. Construction of a novel mRNA-miRNA-lncRNA network and identification of potential regulatory axis associated with prognosis in colorectal cancer liver metastases. Aging (Albany NY). 2021;13(11):14968.
26. Orozco LD, Owen LA, Hofmann J, Stockwell AD, Tao J, Haller S, et al. A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration. Cell genomics. 2023;3(6).
27. Wang H, Wang C, Yao Y, Duan J, Liang Y, Shang Q. Analysis of long noncoding RNAs in the aqueous humor of wet age-related macular degeneration. Exp Eye Res. 2023;234(14):109576.
28. Grothey A, Fakih M, Tabernero J. Management of BRAF-mutant metastatic colorectal cancer: a review of treatment options and evidence-based guidelines. Ann Oncol. 2021;32(8):959–67.
29. Guo F, Li L, Yang W, Hu J fan, Cui J. Long noncoding RNA: a resident staff of genomic instability regulation in tumorigenesis. Cancer Lett. 2021;503:103–9.
30. Huo X, Han S, Wu G, Latchoumanin O, Zhou G, Hebbard L, et al. Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma: implications for tumorigenesis, disease progression, and liver cancer stem cells. Mol Cancer. 2017;16(5):1–10.
31. Li Y, Chen J, Zhang J, Wang Z, Shao T, Jiang C, et al. Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer. Oncotarget. 2015;6(28):25003.
32. Liu Z, Liu L, Weng S, Guo C, Dang Q, Xu H, et al. Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer. Nat Commun. 2022;13(1):816.
33. Zhang X, Wang J, Li J, Chen W, Liu C. CRlncRC: a machine learning-based method for cancer-related long noncoding RNA identification using integrated features. BMC Med Genomics. 2018;11:99–112.
34. Dastmalchi N, Safaralizadeh R, Nargesi MM. LncRNAs: potential novel prognostic and diagnostic biomarkers in colorectal cancer. Curr Med Chem. 2020;27(30):5067–77.
35. He J, Wu F, Han Z, Hu M, Lin W, Li Y, et al. Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of colorectal cancer—from the body fluid to tissue level. Front Oncol. 2021;11:632834.
36. Pan K, Xie Y. LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca2+-FAK signal pathway. Cell Death Dis. 2020;11(6):434.
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| Biomarker Colorectal cancer C6orf223 lncRNA MicroRNAs | ||
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How to Cite
1.
Tutunchi S, Javanmard A-R, Panahi G, M. Soltan B, Akbari A, Ghaderian SMH. Elucidating the Molecular Pathways of Long Noncoding RNA C6orf223 in Colorectal Cancer via microRNA Interactions and Transcriptomic Profiling. Iran J Allergy Asthma Immunol. 2025;:1-12.
