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Published on: April 2, 2020
Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
Zongren Wan1, Jipeng Wang1, Qing Liu1
1Department of Respiratory and Critical Care Medicine, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huanghe West Road, Huaiyin District, Huai'an City, Jiangsu Province, 223300, China.
Abstract:
Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases and is considered as the most common type of cancer. DLX4 was originally identified as a β-globin gene suppressor in red blood cells, which plays critical roles in several types of cancers. However, the role and related mechanism of DLX4 in NSCLC are still unclear. The study aimed to uncover the expression of DLX4 in human NSCLC cells and tissues, reveal its possible role in NSCLC, and investigate the underlying mechanisms. Immunoblot and TCGA database were used to detect the expression of DLX4 in human NSCLC cells and tissues. CCK-8, colony formation, and FCM assays were conducted to detect the effects of DLX4 on the viability and cell cycle of NCI-H2170 and A549 cells. Immunoblot assays were further performed to investigate the possible mechanism underlying DLX4 affecting the growth of NSCLC. We revealed that knockdown of DLX4 inhibited NSCLC cell proliferation. We further revealed that DLX4 knockdown induced the NSCLC cell cycle arrest. Our results further showed that downregulation of DLX4 suppressed YB-1 expression, which further suppressed CKS2 expression, thereby suppressing tumor growth of NSCLC. In conclusion, DLX4 has the potential to serve as a promising drug for NSCLC treatment.
Insights
Downregulating DLX4 inhibits non-small cell lung cancer (NSCLC) proliferation and induces cell cycle arrest. This suggests DLX4 is a potential therapeutic target for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) is the most common cancer type, accounting for 85% of all lung cancer cases.
- DLX4, a known suppressor of the β-globin gene, has roles in various cancers, but its specific function in NSCLC remains largely unknown.
Purpose of the Study:
- To investigate the expression of DLX4 in human NSCLC cells and tissues.
- To elucidate the role and underlying mechanisms of DLX4 in NSCLC progression.
Main Methods:
- DLX4 expression was analyzed using immunoblot assays and The Cancer Genome Atlas (TCGA) database.
- Cell viability, proliferation, and cell cycle were assessed using CCK-8, colony formation, and flow cytometry (FCM) assays.
- Mechanistic investigations involved immunoblot assays to examine protein expression changes.
Main Results:
- Knockdown of DLX4 significantly inhibited NSCLC cell proliferation and induced cell cycle arrest.
- Downregulation of DLX4 led to suppressed YB-1 expression, which in turn reduced CKS2 expression.
- These molecular changes collectively suppressed NSCLC tumor growth.
Conclusions:
- DLX4 plays a critical role in promoting NSCLC cell proliferation and progression.
- The DLX4/YB-1/CKS2 pathway is implicated in NSCLC development.
- DLX4 inhibition presents a promising therapeutic strategy for NSCLC treatment.
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