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Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box
Lin Liu1,2, Pengfei Gong3, Xueling Li1
1Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China.
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.
Insights
Targeting the LINC070974 long noncoding RNA inhibits non-small cell lung cancer (NSCLC) progression and metastasis. siRNA inhalation offers a promising therapeutic strategy for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally.
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- LINC070974 was previously identified as a novel lncRNA associated with tumor cell proliferation.
Purpose of the Study:
- To investigate the functional role of LINC070974 in NSCLC pathogenesis.
- To explore the therapeutic potential of targeting LINC070974 in NSCLC.
- To elucidate the molecular mechanism underlying LINC070974's function.
Main Methods:
- In vitro and in vivo experiments involving LINC070974 knockdown using siRNA.
- Assessment of cell proliferation, migration, and invasion.
- Evaluation of tumor formation in nude mice.
- Analysis of YBX1 recruitment to the CCND1 promoter.
- Nebulized siRNA inhalation delivery for therapeutic intervention.
Main Results:
- Knockdown of LINC070974 significantly inhibited NSCLC cell proliferation, migration, invasion, and tumor formation.
- LINC070974 silencing enhanced cisplatin efficacy in A549/DDP cells.
- LINC070974 regulates YBX1 recruitment to the CCND1 promoter, impacting the p53 signaling pathway.
- Nebulized siRNA targeting LINC070974 effectively prevented tumor metastasis and growth in lung tissues.
Conclusions:
- LINC070974 plays a critical role in promoting NSCLC progression and metastasis.
- Targeting LINC070974 with siRNA, particularly via inhalation, presents a novel and effective therapeutic strategy for NSCLC.
- The findings highlight the therapeutic potential of lncRNAs in lung cancer treatment.
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