Abstract
Background Thyroid carcinoma (THCA) is the most frequent endocrine malignancy. Papillary thyroid carcinoma (PTC) is the major subtype of THCA, accounting for over 80% of all THCA cases. LncRNA PAX8-AS1, a tumor suppressor associated with various human cancers, has been reported to be relevant to the regulation of all sorts of cellular processes. The purpose of this study was to verify the role of PAX8-AS1 in PTC. Methods Three human PTC cell lines (K1, TPC-1, and IHH4) and one normal human thyroid cell line, Nthy-ori3-1, were used in our study. The expression of genes was detected by qRT-PCR. The bioinformatic analysis and luciferase reporter assay were used to confirm the binding relationship of PAX8-AS1 to miR-96-5p, and the targeting relationship of miR-96-5p to PKN2 was also predicted. Cell proliferation and apoptosis capacities were assessed by MTT and flow cytometry, respectively. EdU assay was used to detect cell proliferation. Western blot assay was employed to examine protein expression. Results The expression of PAX8-AS1 was decreased in PTC tissues and cells. PAX8-AS1 overexpression inhibited the proliferation of PTC cells and promoted cell apoptosis. In addition, PAX8-AS1 bonds with miR-96-5p, whose downregulation elevated the expression of PKN2 in PTC cells. Importantly, according to the rescue experiments, PKN2 silencing partially reversed the inhibitory effects of PAX8-AS1 expression on PTC cell proliferation and apoptosis. Conclusions We found that the PAX8-AS1/miR-96-5p/PKN2 axis was closely related to the progression of PTC, which could be a potential target for treating PTC patients.
Highlights
Over the past three decades, an increasing number of people worldwide have been diagnosed with thyroid carcinoma (THCA) [1]
High throughput sequencing technology is developing rapidly in recent years, so that many Long noncoding RNAs (lncRNAs) have been discovered, and numerous research studies have demonstrated that lncRNAs are dysregulated in various cancers [32]. e molecules affected are known as tumor suppressors or oncogenes [33]
LncRNAs are RNA molecules whose transcripts are longer than 200 nt and have no ability to code protein [34]. e roles of PAX8AS1 in different type of cancers as tumor suppressor have been discussed previously [17, 18], which indicated that PAX8-AS1 was downregulated in tumor cells
Summary
Over the past three decades, an increasing number of people worldwide have been diagnosed with thyroid carcinoma (THCA) [1]. Competitive endogenous RNA (ceRNA) network, which represents a new mechanism of interaction between RNAs, plays a crucial role in multiple biological processes and development of tumors [20]. MiR-96-5p was reported to promote the development of many human cancers including PTC. MiR-96-5p overexpression enhances colorectal cancer cell migration and invasion, playing a carcinogenic role in the development of colorectal cancer [25]. Since the ceRNA role of PAX8-AS1 has been reported in breast cancer [27], we suspected that PAX8-AS1 might act as a ceRNA against miR-96-5p in PTC. Our study suggests that PAX8-AS1 may serve as a potential novel prognostic biomarker and therapeutic target for PTC treatment
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