Key Takeaways & Executive Findings
- •• Knockdown of LINC070974 inhibits NSCLC cell proliferation, migration, invasion, and tumor formation in vitro and in vivo. • LINC070974 silencing enhances cisplatin efficacy in drug-resistant A549/DDP cells. • LINC070974 interacts with YBX1 to regulate CCND1 expression and p53 signaling pathway. • Nebulized inhalation of siRNA targeting LINC070974 suppresses lung tumor growth and metastasis, offering a novel therapeutic strategy.
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that knockdown of LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.
1. Introduction
Lung cancer is the leading cause of cancer-related mortality worldwide [1], accounting for approximately one-fourth of all cancer fatalities [2,3], which can be classified into two main subtypes based on its histological morphology: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) [4,5]. NSCLC is the predominant histological subtype, representing approximately 85% of all lung cancer cases [2]. Despite significant therapeutic advances in the treatment of NSCLC over the past two decades, the 5-year relative survival rate remains suboptimal at less than 15% [6].
Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) are a novel class of tumorigenic regulators that play crucial roles in the initiation, maintenance and progression of tumors through multiple mechanisms. Previous studies have revealed that lncRNAs can also serve as predictive, diagnostic and prognostic markers for lung cancer [7‒12]. For example, LINC00472 was found to suppress cell migration and invasion in lung cancer [10]. LINC00312 can induce the migration, invasion, and angiogenesis of lung cancer both in vivo and in vitro [12].
Herein, we identified the long intergenic noncoding RNA LINC070974, which is upregulated in lung adenocarcinoma tissues. We aimed to investigate the role of LINC070974 in the growth and progression of lung cancer cells. We observed that knockdown of LINC070974 significantly inhibited NSCLC cell proliferation, invasion and migration by inhibiting the recruitment of Y-box binding protein 1 (YBX1) to the CCND1 promoter region. Notably, nebulized inhalation of an siRNA against LINC070974 effectively suppressed metastasis and xenograft tumor growth. These findings suggest that LINC070974 could become a promising and effective therapeutic target for treating NSCLC.
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Lin Liu, Pengfei Gong, Xueling Li, Li Zhang, Jiale Niu, Jinhui Zhu, Ziwei Wang, Xingwang Long, Tenghui Cao, Yewen Liu, Ganglin Wang, Tingming Fu, Liang Sun, Wei Li (2026). Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box binding protein 1. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2024093
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Frequently Asked Questions
What is the role of LINC070974 in lung adenocarcinoma?
LINC070974 is a long noncoding RNA that is upregulated in lung adenocarcinoma tissues. Knockdown of LINC070974 inhibits cell proliferation, migration, invasion, and tumor formation, and enhances cisplatin efficacy in resistant cells.
How does LINC070974 interact with YBX1?
LINC070974 interacts with Y-box binding protein 1 (YBX1) and facilitates its recruitment to the CCND1 promoter, thereby regulating cyclin D1 expression and promoting tumor progression.
What is the significance of nebulized inhalation of siRNA in this study?
Nebulized inhalation of siRNA targeting LINC070974 effectively suppresses tumor growth and metastasis in lung tissues, suggesting a promising non-invasive therapeutic approach for NSCLC.
What signaling pathway is involved in LINC070974-mediated effects?
The p53 signaling pathway is mainly involved, as LINC070974 knockdown delays tumor progression through its coregulatory genes that are enriched in this pathway.
What are the potential clinical implications of targeting LINC070974?
Targeting LINC070974 could provide a novel therapeutic strategy for NSCLC, especially for overcoming cisplatin resistance, and the inhalation delivery method offers a patient-friendly approach.
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