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2-methoxyestradiol restrains non-small cell lung cancer tumorigenesis through regulating

Yong Zhang¹, Yuanyuan Mi², Chunhui He³

¹Department of Cardiothoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China.

Thoracic Cancer

|July 13, 2023

Abstract

Background:

Non-small cell lung cancer (NSCLC) is one of the most prevalent and severe malignant tumors in the world and its molecular mechanism is still unclear. In recent years, increasing evidence indicates the significant roles of circRNAs in NSCLC. It has been determined that 2-methoxyestradiol (2-MeOE2) exerts antitumor roles in many cancers. However, the molecular mechanism of 2-MeOE2 in regulating the development of lung cancer needs further elucidation.

Methods:

The expression levels of circ_0010235, microRNA-34a-5p (miR-34a-5p), and nuclear factor of activated T cells 5 (NFAT5) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis and invasion were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry and transwell assays, respectively. The interaction between miR-34a-5p and circ_0010235 or NFAT5 was predicted by bioinformatic software and confirmed by dual-luciferase reporter assay.

Results:

Our data showed 2-MeOE2 hindered cell proliferation, invasion and induced apoptosis in NSCLC, which could be reversed by upregulation of circ_0010235 and NFAT5 or miR-34a-5p knockdown. Circ_0010235 and NFAT5 expression levels were increased, and miR-34a-5p expression level was decreased in NSCLC tissues and cells. In addition, 2-MeOE2 treatment suppressed the expression of circ_0010235 and NFAT5 while promoted the expression of miR-34a-5p. Furthermore, circ_0010235 functioned as a molecular sponge of miR-34a-5p to regulate NFAT5 expression. Knockdown of circ_0010235 or 2-MeOE2 treatment constrained tumor growth in vivo, and circ_0010235 depletion enhanced the inhibitory effect of 2-MeOE2 on tumor growth in vivo.

Conclusion:

These findings demonstrated that 2-MeOE2 retarded NSCLC progression by modulating the circ_0010235/miR-34a-5p/NFAT5 axis, thus providing a new perspective for 2-MeOE2 treatment in NSCLC.

Insights

2-methoxyestradiol (2-MeOE2) inhibits non-small cell lung cancer (NSCLC) progression by targeting the circ_0010235/miR-34a-5p/NFAT5 pathway. This study reveals a novel therapeutic strategy for NSCLC treatment.

Area of Science:

Oncology
Molecular Biology
Biochemistry

Background:

Non-small cell lung cancer (NSCLC) is a prevalent malignancy with unclear molecular mechanisms.
Circular RNAs (circRNAs) play significant roles in NSCLC development.
2-methoxyestradiol (2-MeOE2) exhibits antitumor properties, but its mechanism in lung cancer requires further investigation.

Purpose of the Study:

To elucidate the molecular mechanism of 2-methoxyestradiol (2-MeOE2) in regulating non-small cell lung cancer (NSCLC) progression.
To investigate the role of the circ_0010235/miR-34a-5p/NFAT5 axis in NSCLC.
To explore the potential of 2-MeOE2 as a therapeutic agent for NSCLC.

Main Methods:

Quantitative real-time polymerase chain reaction (qRT-PCR) to detect expression levels of circ_0010235, miR-34a-5p, and NFAT5.
Cellular assays (CCK-8, EdU, flow cytometry, Transwell) to assess proliferation, apoptosis, and invasion.
Bioinformatic analysis and dual-luciferase reporter assays to confirm molecular interactions.

Main Results:

2-MeOE2 inhibited NSCLC cell proliferation and invasion while inducing apoptosis, effects reversed by circ_0010235/NFAT5 upregulation or miR-34a-5p knockdown.
Circ_0010235 and NFAT5 were upregulated, while miR-34a-5p was downregulated in NSCLC tissues and cells.
2-MeOE2 suppressed circ_0010235 and NFAT5 expression and promoted miR-34a-5p expression, with circ_0010235 acting as a sponge for miR-34a-5p to regulate NFAT5.

Conclusions:

2-MeOE2 retards NSCLC progression by modulating the circ_0010235/miR-34a-5p/NFAT5 axis.
This pathway offers a new therapeutic perspective for 2-MeOE2-based treatments in NSCLC.
Targeting this axis may provide novel strategies for NSCLC management.

Read full analysis

Keywords:

2-MeOE2 NFAT5 circ_0010235 miR-34a-5p non-small cell lung cancer

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