A Novel Long Non-Coding Rna, Picsar, Promotes Thyroid Cancer Progression Through the Hsa-Mir-320A/Hsa-Mir-485/Rapgefl1 Axis Publisher



M Hejazi MARYAM ; T Jafari TAHMINEH ; A Yari AMIRHOSSEIN ; R Heshmat RAMIN ; Ba Larijani Bagher A ; S Ahvaz SAMANEH ; O Pourbagherian OMID ; Sm Tavangar Seyed MOHAMMAD ; G Shafiee GITA ; Aa Mokhtarzadeh Amir ALI
Source: Medical Oncology Published:2025

Abstract

Among endocrine cancers, thyroid carcinoma (TC) is the most prevalent and ranks sixth in global mortality rates. Aberrant expression of long non-coding RNA (lncRNAs) is associated with the progression of various human cancers, including TC. The role of PICSAR lncRNA (LINC00162) has been validated in different human cancers. Therefore, this study aimed to assess the expression levels and functions of lncRNA PICSAR in thyroid cancer tumorigenesis. This comprehensive approach combined in silico and in vitro methods to explore the molecular mechanisms and clinical significance of PICSAR in thyroid cancer. This work assessed the expression of the long non-coding RNA LINC00162 and identified differentially expressed genes (DEGs) using the Cancer Genome Atlas (TCGA) database. Interactions among LINC00162, hsa-miR-320A, hsa-miR-485, and RAPGEFL1 were investigated using the LncACT and miRDB databases. Bioinformatics techniques were employed to conduct functional enrichment analysis to clarify the relevant molecular pathways. For the investigation of LINC00162 expression in TC samples, 50 matched samples of thyroid carcinoma and adjacent normal tissue were gathered. Real time PCR was used to objectively evaluate the expression levels of the targeted genes. Every tissue sample was examined pathologically. A specific siRNA was transfected into a thyroid cancer cell line to examine the functional role of LINC00162. The impact of LINC00162 silencing was then assessed by measuring the level of target genes expression following the transfection. Based on TCGA-THCA analysis and qRT-PCR on tissue samples, LINC00162 (PICSAR) was markedly overexpressed in thyroid cancer tissues compared to normal samples. However, no discernible correlation was found between LINC00162 expression and the pathological characteristics of thyroid cancer. Our bioinformatics predictions based on lncRNA-microRNA interactions demonstrate that LINC00162 acts as a molecular sponge for the downregulated microRNAs hsa-miR-320A and hsa-miR-485 in thyroid cancer. RAPGEFL1, a gene associated with the development of thyroid cancer, is upregulated in conjunction with this downregulation. The LINC00162-miRNA-RAPGEFL1 axis is involved in critical carcinogenic processes, including thiamine metabolism, cell cycle control, and folate biosynthesis, according to functional enrichment analysis. Additionally, a bioinformatics study revealed a negative association between PICSAR and the NUDT3 gene, while a positive correlation was found with the SNX18P14 gene. Thyroid cancer cells transfected with LINC00162-specific siRNA showed significant downregulation of LINC00162 and RAPGEFL1, alongside an increase in hsa-miR-320A and hsa-miR-485, ultimately inhibiting the growth of thyroid cancer. These findings suggest that targeting PICSAR may offer a treatment strategy for thyroid cancer by altering important biological processes. In conclusion, LINC00162, which is overexpressed in thyroid cancer, acts as a molecular sponge for hsa-miR-320A and hsa-miR-485, regulating key oncogenic pathways and leading to the upregulation of RAPGEFL1. These effects are reversed upon siRNA-mediated silencing of LINC00162, indicating its potential as a promising therapeutic target for thyroid cancer. RAPGEFL1 regulates the Rap signaling pathway, controlling adhesion, migration, polarity, and metabolism to maintain cellular and tissue homeostasis. Its dysregulation is linked to various diseases, highlighting its potential as a therapeutic target. © 2025 Elsevier B.V., All rights reserved.