Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid tumor type that has a poor prognosis due to its high therapeutic resistance. Since ATC accounts for half of thyroid cancer-related deaths, i Show more
Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid tumor type that has a poor prognosis due to its high therapeutic resistance. Since ATC accounts for half of thyroid cancer-related deaths, it is required to introduce novel therapeutic targets to increase survival in ATC patients. WNT and NOTCH signaling pathways are the pivotal regulators of cell proliferation and migration that can be regulated by microRNAs. We assessed the role of miR-506 in the regulation of cell migration, apoptosis, and drug resistance via NOTCH and WNT pathways in ATC cells. The levels of miR-506 expressions were assessed in ATC cells and tissues. The levels of NOTCH, WNT, and EMT-related gene expressions were also assessed in miR-506 ectopic expressed cells compared with controls. Cell migration and drug resistance were also evaluated to assess the role of miR-506 in the regulation of ATC aggressiveness. There were significant miR-506 down-regulations in ATC cells and clinical samples compared with normal cells and margins. MiR-506 suppressed NOTCH and WNT signaling pathways through LEF1, DVL, FZD1, HEY2, HES5, and HEY2 down-regulations, and APC and GSK3b up-regulations. MiR-506 significantly inhibited ATC cell migration and EMT ( MiR-506 regulated EMT, cell migration, and chemoresistance through regulation of WNT and NOTCH signaling pathways in ATC cells. Therefore, after confirmation with animal studies, it can be introduced as an efficient novel therapeutic factor for ATC tumors. Show less
Notch signaling is an important cellular pathway which affects the development and function of many organs. It plays critical roles in maintaining of progenitor stem cell population as well as balanci Show more
Notch signaling is an important cellular pathway which affects the development and function of many organs. It plays critical roles in maintaining of progenitor stem cell population as well as balancing cell proliferation, survival, differentiation and apoptosis. It has been shown that notch signaling is aberrantly activated during the carcinogenesis of a variety of human cancers. In this study we aimed to explore activation of this signaling pathway in esophageal squamous cell carcinoma (ESCC) through expressional analysis of notch signaling target genes. The mRNA expression of HEY1 and HEY2 was comparatively analyzed by real-time PCR in tumor and related margin normal tissues of 50 ESCC patients. Comparative quantitative real-time PCR indicates the overexpression of HEY1 and HEY2 in 54 and 30% of ESCC samples, respectively. Overexpression of HEY1 was significantly associated with stage of the tumor (p = 0.048) and tumor location (p = 0.008). HEY2 overexpression was also significantly correlated to node metastasis of tumor cells (p = 0.043). Overexpression of HEY1 and HEY2 in ESCC is correlated to different indices of poor prognosis and it is extrapolated that such overexpression is important in progression and development of ESCC tumorigenesis. To the best of our knowledge, this is the first report introducing aberrant activation of notch signaling target genes in ESCC, where it plays roles in development and progression of the malignancy and may be considered in therapeutic modalities to restrict ESCC progression. Show less