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eISSN: 1643-3750

Role of Lin28A/let-7a/c-Myc Pathway in Growth and Malignant Behavior of Papillary Thyroid Carcinoma

Jiaqi Huang, Haishan Lin, Muxun Zhong, Jiexiong Huang, Shuming Sun, Ling Lin, Yongsong Chen

(Department of Endocrinology, The First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China (mainland))

Med Sci Monit 2018; 24:8899-8909

DOI: 10.12659/MSM.908628

Published: 2018-12-09


BACKGROUND: Lin28 is a gene involved in many biological processes, including development, glucose metabolism, and tumorigenesis. Let-7 miRNA is a tumor-suppressor gene that is frequently inactivated in cancer cells. The role of c-Myc (a target gene of let-7) and the Lin28-let-7-c-Myc pathway in the growth and malignancy of thyroid cancer is unclear. The purpose of the present study was to evaluate the expression of Lin28A, let-7a, and c-Myc in human papillary thyroid carcinoma (PTC) and to investigate their potential mechanisms in the progression of PTC.
MATERIAL AND METHODS: Lin28A and c-Myc expression were assessed in PTC tissues and PTC cell lines using immunohistochemistry, Western blotting, and real-time PCR. CCK-8 and Transwell assays were performed to evaluate PTC cell proliferation, migration, and invasion in cells in which the expression of Lin28A was downregulated by RNA interference or in which let-7a was overexpressed after transfection with let-7a mimics.
RESULTS: The expression of Lin28A and c-Myc was upregulated in PTC tissues and cell lines, whereas the expression of let-7a was downregulated in PTC cell lines. Clinically, Lin28A was linked to a higher tumor/node/metastasis stage and the presence of lymph node metastases. Moreover, knockdown of Lin28A activated let-7a processing and inhibited the expression of the downstream gene c-Myc, suppressing cell proliferation, migration, and invasion. Similar results were obtained after let-7a overexpression.
CONCLUSIONS: The Lin28A/let-7a/c-Myc pathway is involved in cancer growth and malignant behavior in PTC and is a potential target for therapeutic intervention in this disease.

Keywords: Genes, myc, MicroRNAs, RNA-Binding Proteins, Thyroid Neoplasms



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