LncRNA CASC9 facilitates papillary thyroid cancer development and doxorubicin resistance via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway

Sep 21, 2026

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Papillary thyroid cancer is a malignant disease threatening human health, and long noncoding RNA CASC9 is implicated as an oncogene in multiple tumors. This study investigates how LncRNA CASC9 regulates doxorubicin resistance in papillary thyroid cancer. CASC9, miR-28-3p, and BCL-2 levels are measured in patient tissues and doxorubicin-resistant cells, with cellular phenotypes assessed by proliferation, apoptosis, migration, and IC50 assays. Mechanistic validation uses dual-luciferase reporter and rescue approaches, including in vivo xenograft experiments.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Background and clinical context

Role of noncoding RNAs and lncRNAs

Methods

Expression and molecular assays

Functional assays and phenotypic measurements

Target verification and rescue experiments

In vivo xenograft validation

Yu etal. Journal of Cardiothoracic Surgery (2024) 19:629 [https://doi.org/10.1186/s13019-024-03129-4](https://doi.org/10.1186/s13019-024-03129-4) Journal of Cardiothoracic Surgery RESEARCH Open Access LncRNA CASC9 facilitates papillary thyroid cancer development and doxorubicin resistance via miR-28-3p/BCL-2 axis and PI3K/ AKT signaling pathway Jianping Yu 1, Chun He 1, Yun Peng 1, YuzhongWen 1 and Jing Wang2* Abstract Background Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC. Methods The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) . CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2 . Rescue experiments were applied to verify the mechanism of CASC9 . Finally, the role of CASC9 was verified by xenograft modeling in vivo. Results We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/ Dox) . Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9 . MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2 . Conclusion CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway. Keywords Papillary thyroid cancer, lncRNA CASC9, miR-28-3p, BCL-2, Doxorubicin *Correspondence: Jing Wang [wangjingnc68@163.com](wangjingnc68@163.com) 1Thyroid Surgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi 341000, China 2Intensive Care Unit, Ganzhou People’s Hospital, No.16 Meiguan Avenue, Zhanggong District, Ganzhou, Jiangxi 341000, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Yu et al. Journal of Cardiothoracic Surgery (2024) 19:629 Introduction Thyroid cancer is the most common endocrine malignancy, accounting for 95% of endocrine tumors. Its incide

FAQs

What is the main purpose of studying LncRNA CASC9 in papillary thyroid cancer?

To explore the mechanism by which LncRNA CASC9 regulates doxorubicin resistance in papillary thyroid cancer.

How did the study assess doxorubicin resistance and related cellular behaviors?

It determined CASC9, miR-28-3p, and BCL-2 expression and used CCK-8, colony formation, flow cytometry, and transwell assays to evaluate IC50, proliferation, apoptosis, and migration.

What signaling pathway and molecular axis are implicated in CASC9’s effect?

CASC9 promotes tumor progression by activating the PI3K/AKT signaling pathway and acts through the miR-28-3p/BCL-2 axis.

Sep 21, 2026

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