No abstract

Background: Autophagy is a stress response mechanism that causes cellular components to degrade. Its defects were associated with multiple pathologies, including cancers. Thyroid cancer is known to be the most prevalent form of malignant neoplasm among endocrine tumors. The aim of the study was to seek and comprehensively explore the role of autophagy related genes and proteins play in thyroid cancers through bioinformatics analysis with their detection in the tissue samples. Methods: Bioinformatics analysis was performed to investigate autophagy related proteins and genes involvement in thyroid cancer progression. The experimental verification was done in cancer samples of one hundred and three patients with thyroid pathology included in the study. The miR-125blevel was detected by PCR in real time. Results and discussion: The bioinformatics analysis verified the miR-125b as a regulatory mechanism in autophagy. Its expression in patients with PTC was reduced by 6.75 times in cancer patients compared to the patients with benign tumors. The BRAFV600E mutations were associated with a decrease in hsa-miR-125b expression by 12.67 times compared to tumors with the wild-type gene. Conclusions: Our findings revealed involvement of the autophagy related proteins in cancer progression. The significant mechanisms of regulation are non-coding RNA sequences implicated in a variety of oncogenic processes. We found that miR-125b is a potential maker in thyroid cancer invasion, BRAV600E mutational status and risk of recurrence.

Autophagy is an important intracellular process that supports cell death and survival. Oncogenesis is associated with a change in the AKT/mTOR signaling pathway status. At the same time, the existence of protective autophagy, as one of the mechanisms of disease progression and the formation of resistance to treatment, has been proven. The review describes the significant mechanisms of the autophagy development, its association with AKT/mTOR signaling pathway. A molecule mTOR in TORC1 complex is associated with the oncogenesis, it provides the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The participation of this phenomenon at all stages of carcinogenesis, influencing on the main signal kinases: AKT, mTOR, is noted. It is shown that in most cases this mechanism is responsible for the progression of the disease and the development of resistance to treatment. The development of thyroid cancer associated with the BRAF mutation and with the activation of the RET oncoprotein, as well as with the formation of radio-resistant forms of the disease is associated with molecular peculiarities of autophagy. Given the inconsistency of this phenomenon regarding their influence on the processes of oncogenesis, its role in the development of thyroid cancer is still unknown.