The role of P62 in the development of human thyroid cancer and its possible mechanism

• Published in: Cancer genetics Vol. 256-257; pp. 5 - 16
• Main Authors: Mao, Ying, Deng, Shou-Jun, Su, Yan-Jun, Diao, Chang, Peng, Ying, Ma, Jun-Feng, Cheng, Ruo-Chuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2021
• Subjects: Apoptosis - genetics; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; NF-kappa B - metabolism; NF-kappaB-Inducing Kinase; NF-κB signaling pathway; P62; Papillary thyroid carcinoma; Protein Serine-Threonine Kinases - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; Signal Transduction; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Up-Regulation - genetics; P62; Papillary thyroid carcinoma; NF-κB signaling pathway
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2021.02.008

•This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway.•p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.•This study shows that p62 is closely related to clinical indicators such as BRAF (V600E) mutation, lymph node metastasis and multiple lesions, and can be further studied as an indicator of clinical pathology analysis. Thyroid cancer is the most common malignancy in human endocrine system. Increasing evidence has indicated that p62 plays a key role in tumorigenesis. The roles and underlying molecular mechanisms of P62 in thyroid cancer, however, remain to be elucidated. The expression levels of P62 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of P62 on thyroid cancer cell proliferation, migration, invasion, cell cycle and apoptosis were measured by CCK-8 assay, transwell assay, flow cytometry and transwell assay, respectively. In terms of the mechanism, P62 could stimulate thyroid cancer progression by the activation of nuclear factor-kappa B (NF-κB) signaling pathway. P62 was highly expressed in thyroid tumor tissues. Furthermore, high expression of p62 was observed in PTC cell lines, and especially in the K1 and TPC-1 cells. In vitro, the up-regulation of p62 promoted cell proliferation, migration, and invasion of thyroid cancer cells, whereas the knockdown of p62 resulted in the opposite effect. Knock-down of P62 increased the number of cells in the G0/G1 phase but reduced it in the S and G2/M phase. Moreover, we confirmed that overexpression of p62 inactivated NF-κB pathway with sequencing analysis and bioinformatics analysis. This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.