Abstract
Long noncoding RNAs (lncRNAs) are emerging as important regulators in the development of cancer cells. However, the role and mechanisms of most lncRNAs in papillary thyroid carcinoma (PTC) remain unknown. In this study, we investigated lncRNA expression profiles of PTC using RNA-seq in two groups of PTC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 53 pairs of tissues. We identified a novel lncRNA, n384546, which is highly expressed in PTC tissues and cell lines. n384546 expression was associated with clinicopathological features of PTC patients, such as tumor size, lymph node metastasis, and TNM stage. Functionally, knockdown of n384546 inhibited PTC cell proliferation, invasion, and migration both in vitro and in vivo. In addition, we identified miR-145-5p as a key miRNA target of n384546 using online bioinformatics tools. Anti-miR-145 could partially reverse the effects of n384546 knockdown. Furthermore, we found that n384546 could regulate the expression of AKT3 by sponging miR-145-5p, which was confirmed using an in vitro luciferase assay. In conclusion, we validated n384546 as a novel oncogenic lncRNA in PTC and determined that the n384546/miR-145-5p/AKT3 pathway contributes to PTC progression, which might be used as potential therapeutic targets for PTC patients.
Highlights
Thyroid cancer is the most common endocrine malignancy, and its incidence worldwide has increased rapidly over past several decades
The 5-year overall survival rate of papillary thyroid carcinoma (PTC) patients is about 95%, tumors can metastasize into distant organs and lymph nodes, resulting in poor prognosis and high reoccurrence in some patients[3,4]
To validate RNA sequencing (RNA-seq) results, we selected seven upregulated Long noncoding RNAs (lncRNAs) and seven downregulated lncRNAs with high differential expression and analyzed their relative expression levels in the tissues of the same patients which were used for the RNA-seq study (16 pairs of PTC and corresponding normal thyroid tissues) using quantitative real-time PCR (qRT-PCR)
Summary
Thyroid cancer is the most common endocrine malignancy, and its incidence worldwide has increased rapidly over past several decades. In China, incidence of thyroid cancer is 6.6 per 100,000 persons according to the Chinese Cancer Registry, and thyroid cancer has become the sixth most common malignant tumor in the female population of China[1]. Most patients with PTC can be cured by traditional clinical managements such as thyroidectomy, radioiodine, or TSH suppression therapy. The 5-year overall survival rate of PTC patients is about 95%, tumors can metastasize into distant organs and lymph nodes, resulting in poor prognosis and high reoccurrence in some patients[3,4]. It is of great importance to investigate the underlying molecular mechanisms to improve the diagnosis and prognosis of PTC patients
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