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JMJD2C-mediated long non-coding RNA MALAT1/microRNA-503-5p/SEPT2 axis worsens non-small cell lung cancer
Jun Zhang1, Mingliang Wang1, Jiashun Wang1
1Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
Abstract:
Jumonji domain containing protein 2C (JMJD2C) could epigenetically regulate cancer cells. We specifically explored the downstream mechanism of JMJD2C in non-small cell lung cancer (NSCLC) from the long non-coding RNA metastasis associated with lung adenocarcinoma transcript 1/microRNA-503-5p/septin 2 (MALAT1/miR-503-5p/SEPT2) axis. NSCLC clinical tissues were utilized to assess JMJD2C, MALAT1, miR-503-5p and SEPT2 levels. NSCLC cell lines (A549 and H1299) were applied for loss-of-function and gain-of-function tests to identify the functional roles of JMJD2C, MALAT1, miR-503-5p, and SEPT2. The interactions among JMJD2C, MALAT1, miR-503-5p, and SEPT2 were assessed. Augmented JMJD2C, MALAT1, and SEPT2 and reduced miR-503-5p levels were found in NSCLC. Depleting JMJD2C or MALAT1, or restoring miR-503-5p exerted anti-tumor effects on NSCLC cells in vitro and in vivo. JMJD2C is bound to the promoter of MALAT1. MALAT1 bound to miR-503-5p and miR-503-5p targeted SEPT2. Knocking down MALAT1 or SEPT2, or elevating miR-503-5p mitigated the pro-tumor effects of upregulated JMJD2C on NSCLC. It is evident that the JMJD2C-mediated MALAT1/miR-503-5p/SEPT2 axis takes part in the process of NSCLC and even worsens NSCLC.
Insights
Jumonji domain containing protein 2C (JMJD2C) epigenetically regulates non-small cell lung cancer (NSCLC) via the MALAT1/miR-503-5p/SEPT2 axis. Targeting this pathway offers a potential therapeutic strategy for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Jumonji domain containing protein 2C (JMJD2C) is implicated in epigenetic regulation within cancer.
- Non-small cell lung cancer (NSCLC) progression involves complex molecular mechanisms.
- Understanding downstream pathways of JMJD2C is crucial for NSCLC research.
Purpose of the Study:
- To elucidate the downstream mechanism of JMJD2C in NSCLC.
- To investigate the role of the long non-coding RNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1)/microRNA-503-5p (miR-503-5p)/septin 2 (SEPT2) axis in NSCLC.
- To assess the interactions between JMJD2C, MALAT1, miR-503-5p, and SEPT2 in NSCLC.
Main Methods:
- Analysis of JMJD2C, MALAT1, miR-503-5p, and SEPT2 levels in NSCLC clinical tissues.
- Loss-of-function and gain-of-function experiments in NSCLC cell lines (A549, H1299).
- Assessment of molecular interactions using various assays.
Main Results:
- Elevated JMJD2C, MALAT1, and SEPT2, with decreased miR-503-5p, observed in NSCLC.
- JMJD2C depletion or MALAT1 knockdown, or miR-503-5p restoration, exhibited anti-tumor effects in vitro and in vivo.
- JMJD2C directly binds to the MALAT1 promoter; MALAT1 interacts with miR-503-5p; miR-503-5p targets SEPT2.
- Modulating MALAT1, SEPT2, or miR-503-5p counteracted JMJD2C-induced pro-tumor effects.
Conclusions:
- The JMJD2C-mediated MALAT1/miR-503-5p/SEPT2 axis is a key player in NSCLC pathogenesis.
- This axis contributes to NSCLC progression and severity.
- Targeting the JMJD2C-MALAT1/miR-503-5p/SEPT2 pathway presents a potential therapeutic avenue for NSCLC.
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