بررسي نقش ژن ليزوزومي CTSC در سرطان تيروئيد پاپيلاري

Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine system. Given the evidence from previous studies demonstrating increased CTSC expression in various cancers an‎d its potential role in the regulation of autophagy, oxidative stress, an‎d apoptosis, as well as the reported upregulation of CTSC in PTC based on immunohistochemical analysis, CTSC was selec‎ted as the target gene of this study from among the common genes identified through bioinformatic analysis of microarray datasets with lysosomal functions, following the observation of its association with lymph node metastasis. The aim of this study was to eva‎luate changes in CTSC gene expression in PTC tumor tissue compared with adjacent normal tissue an‎d to investigate the effect of treatment with all-trans retinoic acid (ATRA) on the expression level of this gene an‎d, subsequently, on the biological behavior of PTC cells. This study was conducted in two phases: bioinformatic an‎d experimental. First, using microarray an‎d RNA sequencing data, CTSC expression levels were eva‎luated in PTC tumor tissues compared with normal tissues. In the experimental phase, B-CPAP cells were treated with ATRA to eva‎luate changes in CTSC expression an‎d their cellular consequences. CTSC expression was assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, the effects of ATRA on cell viability, intracellular reactive oxygen species (ROS) accumulation, an‎d cell migration were eva‎luated using the MTT assay, DCFDA staining followed by flow cytometry, an‎d the scratch assay, respectively. Bioinformatic analyses demonstrated that CTSC expression was significantly increased in PTC samples compared with normal tissues, an‎d this upregulation was positively associated with lymph node metastasis. The experimental analyses further confirmed the increased expression of CTSC in PTC tumor tissue compared with adjacent normal tissue. Treatment of B-CPAP cells with ATRA resulted in a significant an‎d concentration-dependent reduction in cell viability, as well as a significant decrease in CTSC expression. ATRA treatment was also associated with increased intracellular ROS levels an‎d reduced migratory capacity of B-CPAP cells. Overall, the findings of this study demonstrated: (a) increased CTSC expression in fresh PTC tumor tissue compared with adjacent normal tissue an‎d (b) a concomitant decrease in CTSC expression an‎d aggressive tumor-related behavior in ATRA-treated B-CPAP cells. Therefore, the findings suggest that CTSC may be associated with the maintenance an‎d progression of tumorigenic characteristics in PTC.

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