LEM domain containing 1 promotes thyroid cancer cell proliferation and migration by activating the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition.

Abstract

Thyroid cancer (TC) is the most common type of endocrine malignancy in humans, and its relative incidence has increased continuously in recent years. However, the primary molecular mechanisms of thyroid tumorigenesis and progression remain unclear. Papillary TC (PTC) is the most common subtype of TC. Recent studies have reported that one of the tumorigenesis and progression mechanisms is driven by genetic alterations that regulate the TC cell signaling pathway. In the present study, RNA sequencing (RNA-seq) was performed on 79 paired PTC and adjacent normal thyroid tissues to further study the molecular mechanisms of TC. Reverse transcription-quantitative PCR was used to detect the expression levels of LEM domain containing 1 (LEMD1) in 47 paired PTC and adjacent normal thyroid tissue samples. Initial analysis revealed that LEMD1 expression was significantly upregulated in TC tissues compared with that in normal tissues. The results of the thyroid RNA-seq datasets from The Cancer Genome Atlas were consistent with the RNA-seq analysis results of the present study. High LEMD1 expression increased the risk of lymph node metastasis in patients with TC. The biological function of LEMD1 on cell proliferation, migration, invasion and apoptosis was investigated in vitro via small interfering RNA and overexpression vector. Gene set enrichment analysis indicated that high LEMD1 expression was associated with epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Western blotting revealed that LEMD1 modulated the protein expression levels of E-cadherin, N-cadherin, vimentin, β-catenin and cleaved-caspase 3. In conclusion, the present results indicated that LEMD1 may drive TC cell tumorigenesis and progression by activating the Wnt/β-catenin signaling pathway and EMT.