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09 December 2018 : Laboratory Research  

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

Jiaqi Huang1ABCDEF, Haishan Lin1ABCD, Muxun Zhong1ABCD, Jiexiong Huang2BD, Shuming Sun3B, Ling Lin4ADEFG, Yongsong Chen1ADEFG*

DOI: 10.12659/MSM.908628

Med Sci Monit 2018; 24: LBR8899-8909

Abstract

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, RNA-Binding Proteins, Thyroid Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750