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circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
Changpeng Sun1, Hongjun Guan2, Jinjin Li2
1Department of Cardiothoracic Surgery, Jianhu Clinical Medical College of Yangzhou University, No. 666, Nanhuan Road, Jinhu Town, Jianhu, Yancheng City, Jiangsu Province, 224700, PR China.
Abstract:
Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancers, which are the main killer of cancer-related death worldwide. Circular RNA (circRNA) has been found to modulate NSCLC development. However, the role of circ_0000376 in NSCLC development has been underreported. The present work showed that circ_0000376 and 3-phos-phoinositide-dependent protein kinase-1 (PDPK1) expression were dramatically increased, but miR-545-3p was decreased in NSCLC tissues and cells. circ_0000376 expression was closely associated with lymph node metastasis, tumor-node-metastasis stage, and tumor size of NSCLC patients. circ_0000376 knockdown repressed NSCLC cell proliferation, migration, invasion, and glutaminolysis but induced cell apoptosis. Additionally, miR-545-3p bound to circ_0000376, and circ_0000376 regulated cell phenotypes by associating with miR-545-3p. MiR-545-3p also participated in NSCLC cell proliferation, migration, invasion, apoptosis, and glutaminolysis by targeting PDPK1. Further, circ_0000376 absence repressed tumor formation in vivo. Collectively, circ_0000376 regulated NSCLC cell tumor properties by the miR-545-3p/PDPK1 axis, suggesting that circ_0000376 could be employed as a therapeutic target for NSCLC.
Insights
Circular RNA circ_0000376 promotes non-small cell lung cancer (NSCLC) progression by regulating the miR-545-3p/PDPK1 pathway. Targeting circ_0000376 offers a potential therapeutic strategy for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- The specific function of circ_0000376 in NSCLC remains largely unexplored.
Purpose of the Study:
- To investigate the role and mechanism of circ_0000376 in non-small cell lung cancer (NSCLC).
- To explore the relationship between circ_0000376, miR-545-3p, and PDPK1 in NSCLC progression.
Main Methods:
- Analysis of circ_0000376 and PDPK1 expression levels in NSCLC tissues and cells.
- Assessment of miR-545-3p expression in NSCLC.
- Investigation of the correlation between circ_0000376 expression and clinical parameters.
- Functional assays including cell proliferation, migration, invasion, apoptosis, and glutaminolysis.
- In vivo tumor formation experiments.
Main Results:
- Circ_0000376 and PDPK1 expression were significantly upregulated, while miR-545-3p was downregulated in NSCLC.
- Circ_0000376 expression correlated with lymph node metastasis, TNM stage, and tumor size.
- Knockdown of circ_0000376 inhibited NSCLC cell proliferation, migration, invasion, and glutaminolysis, while inducing apoptosis.
- Circ_0000376 acts as a sponge for miR-545-3p, which targets PDPK1, thereby regulating NSCLC phenotypes.
- Circ_0000376 knockdown suppressed tumor growth in vivo.
Conclusions:
- Circ_0000376 promotes NSCLC progression through the miR-545-3p/PDPK1 axis.
- Circ_0000376 represents a potential diagnostic biomarker and therapeutic target for NSCLC.
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