Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/<i>FN1</i>/PI3K-AKT signaling pathway

Considering the resistance of papillary thyroid cancer (PTC) ¹³¹I therapy, this study was designed to find a solution at molecular respect. By probing into lncRNA-NEAT1/miR-101-3p/<i>FN1</i> axis and PI3K/AKT signaling pathway, this study provided a potential target for PTC therapy. ¹³¹I-resistant cell lines were established by continuous treatment with median-lethal ¹³¹I. Bioinformatic analysis was applied to filtrate possible lncRNA/miRNA/mRNA and related signaling pathway. Luciferase reporter assay was employed in the verification of the targeting relationship between lncRNA and miRNA as well as miRNA and mRNA. MTT assay and flow cytometry assay were performed to observe the impact of NEAT1/miR-101-3p/<i>FN1</i> on cell viability and apoptosis in radioactivity iodine (RAI)-resistant PTC cell lines, respectively. Western blot and qRT-PCR were conducted to measure the expression of proteins and mRNAs in RAI-resistant PTC tissues and cells. Meanwhile, endogenous PTC mice model were constructed, in order to verify the relation between NEAT1 and RAI-resistance <i>in vivo</i>. NEAT1 was over-expressed in RAI-resistant PTC tissues and cell lines and could resist RAI by accelerating proliferation accompanied by suppressing apoptosis. It indicated that overexpressed NEAT1 restrained the damage of RAI to tumor in both macroscopic and microcosmic. Besides, NEAT1/miR-101-3p exhibited a negative correlation by directly targeting each other. The expression of <i>FN1</i>, an overexpressed downstream protein in RAI-resistance PTC tissues, could be tuned down by miR-101-3p, while the decrease could be restored by NEAT1. In conclusion, both <i>in vitro</i> and <i>in vivo</i>, NEAT1 suppression could inhibit ¹³¹I resistance of PTC by upregulating miR-101-3p/<i>FN1</i> expression and inactivated PI3K/AKT signaling pathway both <i>in vitro</i> and <i>in vivo</i>.