LncRNAs as Diagnostic Biomarkers for Thyroid Carcinoma
Salman Hasan
Introduction. Thyroid carcinoma is a grouped term for a class of 5 different thyroid gland cancers that are mainly benign and highly treatable2. However, Thyroid carcinoma is one of the most misdiagnosed disorders globally with a rate of 500% overdiagnosis in the US alone1. Accompanying this high rate is an incredible waste of resources on unnecessary imaging and physician visits that can be better utilized in other ways. Long non-coding RNAs have been demonstrated to have integral role in cell proliferation, differentiation, and migration in multiple cancers4. Studies have shown that certain LncRNAs (MEG3, BRAF) are also complicit in the proliferation of thyroid carcinomas. Methods. Retroviral plasmids combined with a MEG3 vector were used to transfect thyroid cancer cells. A migration assay was then conducted in which the cells were observed to detect movement through transwells via pores towards a medium containing 10% FBS, a chemoattractant. Western blot analysis was utilized to determine expression levels of MEG3 in the different colonies5. The BRAF assays were conducted by utilizing Thyroid carcinoma biopsies and subsequently extracting DNA. The specimens were then analyzed using PCR to amplify the V600E point mutation commonly found in the BRAF gene6. Results. In regard to the MEG3 assays, there was a statistically significant difference in the number of colonies with metastatic potential in relation to the expression levels of MEG3. The colonies with decreased levels of MEG3 were demonstrated to have a higher metastatic potential5. In reference to the BRAF assays, statistical analysis showed that individuals with BRAF mutations were evident for advanced tumor stages by way of Ras cycle disturbances6. In addition, comparative analyses utilizing DNA sequencing were conducted in both normal tissues and tissues from patients with papillary thyroid carcinoma which populated a list of LncRNAs with deviant amplification levels7. Conclusions. Studies have elucidated that perturbance in LncRNAs normal activity is associated with carcinoma inception and proliferation, with strains specific for thyroid carcinoma. The wastage of resources on cases that result in false positives for Thyroid carcinoma can be reduced by potentially developing a screening method to detect aberrant LncRNAs before invasive and costly imaging and procedures are conducted.
- Review- Maniakas, A., Davies, L., & Zafereo, M. E. (2018). Thyroid Disease Around the World. Otolaryngologic Clinics of North America. doi:10.1016/j.otc.2018.01.014
- Review- Massimino M, Evans DB, Podda M, et al. Thyroid cancer in adolescents and young adults. Pediatr Blood Cancer. 2018;e27025. https://doi.org.ezproxy.library.tamu.edu/10.1002/pbc.27025
- Primary- Sun, Honggang, et al. “LncRNA CRNDE promotes cell proliferation, invasion and migration by competitively binding miR-384 in papillary thyroid cancer.” Oncotarget, vol. 8, no. 66, Jan. 2017, doi:10.18632/oncotarget.22819.
- Review- Jing, W., Li, X., Peng, R., Lv, S., Zhang, Y., Cao, Z., . . . Ming, L. (2018). The diagnostic and prognostic significance of long noncoding RNAs expression in thyroid cancer: A systematic review and meta-analysis. Pathology – Research and Practice,214(3), 327-334. doi:10.1016/j.prp.2018.01.008
- Wang, C., Yan, G., Zhang, Y., Jia, X., & Bu, P. (2015). Long non-coding RNA MEG3 suppresses migration and invasion of thyroid carcinoma by targeting of Rac1. Neoplasma,62(04), 541-549. doi:10.4149/neo_2015_065
- Mahdi Daliri, Mohammad Reza Abbaszadegan, Mostafa Mehrabi Bahar, Azadeh Arabi, Mona Yadollahi, Azar Ghafari, Negin Taghehchian & Seyed Rasoul Zakavi(2014)The role of BRAF V600E mutation as a potential marker for prognostic stratification of papillary thyroid carcinoma: a long-term follow-up study,Endocrine Research,39:4,189-193,DOI: 3109/07435800.2013.879169
- Liyanarachchi, S., Li, W., Yan, P., Bundschuh, R., Brock, P., Senter, L., … He, H. (2016). Genome-Wide Expression Screening Discloses Long Noncoding RNAs Involved in Thyroid Carcinogenesis. The Journal of Clinical Endocrinology and Metabolism, 101(11), 4005–4013.