Overexpression of PAX8-AS1 Inhibits Malignant Phenotypes of Papillary Thyroid Carcinoma Cells via miR-96-5p/PKN2 Axis

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.

LncRNA-PAX8-AS1 Silencing Decreases Cell Viability, Enhances Apoptosis, and Suppresses Doxorubicin Resistance in Myeloid Leukemia via the miR-378g/ERBB2 Axis

“…ADM resistance mainly causes apoptosis failure in cytostatic treatment of haemoblastosis, leading to chemoresistance in AML [ 47 ]. Zhou's study recorded that PAX8-AS1 positively correlates with the apoptosis of papillary thyroid carcinoma cells [ 48 ]. In some way, our results contradict Zhou's finding by demonstrating that PAX8-AS1 overexpression inhibited apoptosis of HL60 cells.…”

Association of LncRNA-PAX8-AS1 and LAIR-2 polymorphisms along with their expression with clinical and subclinical hypothyroidism

“…Moreover, in adult thyroid, PAX8 transcription factor was regarded as a master regulator of the differentiated thyroid phenotype by overlapping with genomic binding sites such as promoter regions and boundary elements close to the 5'-UTRs of identified genes encoding sodium iodide symporter, thyroid peroxidase, and thyroglobulin, thus activating the expression of these critical proteins for the biosynthesis, storage, and secretion of thyroid hormones; T3 and T4 15 , 28 . Additionally, the expression level of LncRNA-PAX8-AS1 was previously shown to be significantly associated with overall or recurrence-free survival time in patients with papillary thyroid carcinoma 29 . In this study, we identified that downregulation of serum LncRNA-PAX8-AS1 expression level in clinical and subclinical hypothyroidism may predict the risk and help in the diagnosis of hypothyroidism.…”

Construction of miRNA‐lncRNA‐mRNA co‐expression network affecting EMT‐mediated cisplatin resistance in ovarian cancer

“…However, a recent study reported the tumour suppressor role of PAX8‐AS1. 130 PAX8 has a role in transforming the ovarian cancer cell into mesenchymal phenotype. 131 We hypothesize that PAX8‐AS1 may maintain epithelial characteristics in these cells by regulating PAX8.…”

“…Lu et al 129 demonstrated that high expression of PAX8‐AS1 is associated with poor relapse‐free survival in thyroid cancer patients. However, a recent study reported the tumour suppressor role of PAX8‐AS1 130 . PAX8 has a role in transforming the ovarian cancer cell into mesenchymal phenotype 131 .…”