The Role of Long Non-coding RNA (NKILA and LINC00993) as Tumour Biomarkers in Breast Cancer Role of Long Non-coding RNA
Abstract
Background: Long non-coding RNAs (NKILA and LINC00993) are downregulated in breast cancer (BC) and can have potential use as a novel tumor biomarker. The Aim of the work is to investigate the LncRNAs (NKILA and LINC00993) and cytokines (NF-κB and CXCL-1) as potential biomarkers in BC.
Methods: This Cross-sectional study included sixty-four pairs of surgically resected human breast cancer tissues and adjacent breast tissues. Expressions of LncRNAs (NKILA, LINC00993) and (NF-κB, CXCL1) cytokines were detected using real-time quantitative polymerase chain reaction (qPCR) analysis,
Results: There was a significant decrease in LncRNAs (NKILA, LINC00993) levels in tumor tissue compared to normal tissue (P<0.001). Also, there was a significant increase in NF-κB and CXCL1 levels in tumor tissue compared to normal tissue (P<0.001). ROC curve analysis indicated that the LncRNAs (NKILA, LINC00993) expression levels could be considered a promising marker for the diagnosis of breast cancer patients with a sensitivity (90.6%, 92.2% respectively). Also, cytokines (NF-κB and CXCL-1) expression levels could be considered a promising marker for the diagnosis of breast cancer patients with a sensitivity and specificity of 87.5%, and 89.1% respectively).
Conclusion: These findings suggest that LncRNAs (NKILA, LINC00993) and cytokines (NF-κB and CXCL-1) can be used as novel biomarkers for breast cancer.
References
DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, Jemal A, Siegel RL. Breast cancer statistics, 2019. CA Cancer J Clin. 2019 ;69(6):438-451. doi: 10.3322/caac.21583.
Huang J, Chan PS, Lok V, Chen X, Ding H, Jin Y, Yuan J, Lao XQ, Zheng ZJ, Wong MC. Global incidence and mortality of breast cancer: a trend analysis. Aging (Albany NY). 2021 ;13(4):5748-5803. doi: 10.18632/aging.202502.
Ahmed RA and Yussif SM. Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study. J Solid Tumors. 2016; 6(2): 8-16. DOI:10.5430/jst.v6n2P8.
Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. Nat Rev Cancer. 2020;20(8):417-436. doi: 10.1038/s41568-020-0266-x.
Salimimoghadam S, Taefehshokr S, Loveless R, Teng Y, Bertoli G, Taefehshokr N, et al. The role of tumor suppressor short non-coding RNAs on breast cancer. Crit Rev Oncol Hematol. 2021; 158:103210. doi: 10.1016/j.critrevonc.2020.103210.
Dykes IM, Emanueli C. Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA. Genomics Proteomics Bioinformatics. 2017 ;15(3):177-186. doi: 10.1016/j.gpb.2016.12.005.
Schmitt AM, Chang HY. Long noncoding RNAs in cancer pathways. Cancer cell. 2016; 29(4):452-463. doi: 10.1016/j.ccell.2016.03.010.
Guo S, Jian L, Tao K, Chen C, Yu H, Liu S. Novel Breast-Specific Long Non-coding RNA LINC00993 Acts as a Tumor Suppressor in Triple-Negative Breast Cancer. Front Oncol. 2019; 9:1325. doi: 10.3389/fonc.2019.01325.
Singh A, Martinez-Yamout MA, Wright PE, Dyson HJ. Interactions of a Long Noncoding RNA with Domains of NF-κB and IκBα: Implications for the Inhibition of Non-Signal-Related Phosphorylation. Biochemistry. 2022 ;61(5):367-376. doi: 10.1021/acs.biochem.1c00732.
Sobin LH, Gospodarowicz MK, Wittekind, C. TNM Classification of Malignant Tumours, 7th edn, 2010. p. 336, WileyBlackwell, Hoboken, NY
Pal A. Protocols in Advanced Genomics and allied techniques. Springer US; 2022.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492.
Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014; 2014:437971. doi: 10.1155/2014/437971.
Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S. Molecular Characterization and Mortality From Breast Cancer in Men. J Clin Oncol. 2018 ;36(14):1396-1404. doi: 10.1200/JCO.2017.76.8861.
Amelio I, Bernassola F, Candi E. Emerging roles of long non-coding RNAs in breast cancer biology and management. Semin Cancer Biol. 2021 ;72:36-45. doi: 10.1016/j.semcancer.2020.06.019.
Huang D, Chen J, Yang L, Ouyang Q, Li J, Lao L, et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat Immunol. 2018 ;19(10):1112-1125. doi: 10.1038/s41590-018-0207-y.
Luo LH, Rao L, Luo LF, Chen K, Ran RZ, Liu XL. Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway. Microvasc Res. 2020;129:103968. doi: 10.1016/j.mvr.2019.103968.
Bian D, Gao C, Bao K, Song G. The long non-coding RNA NKILA inhibits the invasion-metastasis cascade of malignant melanoma via the regulation of NF-ĸB. Am J Cancer Res. 2017 ;7(1):28-40.
Lu Z, Li Y, Wang J, Che Y, Sun S, Huang J, et al. Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway. J Exp Clin Cancer Res. 2017 ;36(1):54. doi: 10.1186/s13046-017-0518-0.
Tao F, Xu Y, Yang D, Tian B, Jia Y, Hou J, et al. LncRNA NKILA correlates with the malignant status and serves as a tumor-suppressive role in rectal cancer. J Cell Biochem. 2018 ;119(12):9809-9816. doi: 10.1002/jcb.27300.
Chen R, Cheng Q, Owusu-Ansah KG, Song G, Jiang D, Zhou L, et al. a prognostic indicator, inhibits tumor metastasis by suppressing NF-κB/Slug mediated epithelial-mesenchymal transition in hepatocellular carcinoma. Int J Biol Sci. 2020 ;16(3):495-503. doi: 10.7150/ijbs.39582.
Wu W, Chen F, Cui X, Yang L, Chen J, Zhao J, et al. LncRNA NKILA suppresses TGF-β-induced epithelial-mesenchymal transition by blocking NF-κB signalling in breast cancer. Int J Cancer. 2018;143(9):2213-2224. doi: 10.1002/ijc.31605.
Liu B, Sun L, Liu Q, Gong C, Yao Y, Lv X, et al. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer Cell. 2015 ;27(3):370-81. doi: 10.1016/j.ccell.2015.02.004.
Wang N, Liu W, Zheng Y, Wang S, Yang B, Li M, et al. CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling. Cell Death Dis. 2018 ;9(9):880. doi: 10.1038/s41419-018-0876-3.
Chen C, Li Z, Yang Y, Xiang T, Song W, Liu S. Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer. Cancer Biol Ther. 2015;16(6):856-65. doi: 10.1080/15384047.2015.1040957.
Chen C, Yang L, Rivandi M, Franken A, Fehm T, Neubauer H. Bioinformatic Identification of a Breast-Specific Transcript Profile. Proteomics Clin Appl. 2020 ;14(6):e2000007. doi: 10.1002/prca.202000007.
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