MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44

Abstract

Papillary thyroid cancer (PTC) is the most common endocrine malignancy, despite marked achieves in recent decades, the mechanisms underlying the pathogenesis and progression for PTC are incomplete. Accumulating evidence show that γ-glutamylcyclotransferase (GGCT), an enzyme participated in glutathione homeostasis that is elevated in multiple types of tumors, represents an attractive therapeutic target. Using bioinformatics, immunohistochemistry, qRT-PCR and western blot assays, we found that GGCT expression was upregulated in PTC, correlated with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the growth and metastasis ability of PTC cells both in vitro and in vivo and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP2 and MMP9) while increased epithelial marker (E-cadherin) in PTC cells. We confirmed binding of miR-205-5p on the 3’-UTR regions of GGCT by dual luciferase reporter assay, RNA-RNA pull down assay. Delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found GGCT interacted with and stabilized CD44 in PTC cells by co-immunoprecipitation and immunohistochemistry assays. Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.

Functional neuronal circuits promote disease progression in cancer

“…Instead, these sEVs package miR-205-5p, which functions as a tumor suppressor (68), its packaging within sEVs inhibits progression of liver cancer (69), and it is also antitumorigenic in colorectal cancer (70). Consistent with this, miR-205-5p has been shown to regulate pathways important for cell adhesion, angiogenesis, and cell-cell communication (70)(71)(72)(73). We speculate that additional innervation signals (miRNA, neurotrophins, and axonal guidance molecules) are likely shared between HPV − HNSCC and HGSOC and are distinct from those associated with HPV + HNSCC and that, together, these factors dictate the innervation status of these cancers.…”

Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer

“…Our previous study showed that GGCT knockdown reduced the proliferation, migration and invasion abilities of PTC cells in vitro and blocked the EMT process. Mechanistically, it was found that GGCT can bind to CD44 and that GGCT plays a role in stabilizing CD44 to prevent its degradation [ 26 ]. Whether the interaction between GGCT and MRPL9 in this study is based on the modification of MRPL9 by GGCT remains to be further investigated.…”

“…In addition, GGCT is highly expressed in colorectal cancer [ 22 ], gastric cancer [ 23 ], prostate cancer [ 24 ], and human glioma [ 25 ]. Our previous study showed that GGCT is highly expressed in PTC, and knockdown of GGCT inhibited the migration ability of PTC cells [ 26 ]. In this paper, we further explore the molecular mechanism of GGCT regulating the proliferation and migration of PTC cells on the basis of previous research, and provide theoretical support for the treatment of PTC.…”

Proliferation, Metastasis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells in the Expression and Effect of Kiwifruit Extract through the Regulation of miR-205-5p

“…MiR-205-5p functioned as a tumor promoter in many cancers, including ovarian cancer [ 21 ] and lung cancer [ 22 ]. On the contrary, many studies showed that miR-205-5p was downregulated in thyroid cancer, and its upregulation suppressed cell proliferation and invasion [ 23 ]. In an NPC-related study, miR-205-5p had been found to be a tumor promoter [ 9 , 10 ].…”