Available online 15 May 2024, 114093

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Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers with a low five-year survival rate. Therefore, the mechanistic pathways and biomarkers of NSCLC must be explored to elucidate its pathogenesis. In this study, we examined TIPE3 expression in NSCLC cells and investigated the molecular mechanisms underlying NSCLC regulation in vivo and in vitro. We collected tissue samples from patients with NSCLC to examine TIPE3 expression and its association with patient metastasis and prognosis. Furthermore, we evaluated the expression level of TIPE3 in NSCLC cells. Cell lines with the highest expression were selected for molecular mechanism experiments, and animal models were established for in vivo verification. The results showed that TIPE3 was significantly increased in patients with NSCLC, and this increased expression was associated with tumor metastasis and patient prognosis. TIPE3 knockdown inhibited proliferation, migration, invasion, EMT, angiogenesis, and tumorsphere formation in NSCLC cells. Moreover, it reduced the metabolic levels of tumor cells. However, overexpression of TIPE3 has the opposite effect. The in vivo results showed that TIPE3 knockdown reduced tumor volume, weight, and metastasis. Furthermore, the results showed that TIPE3 may inhibit malignant progression of NSCLC via the regulation of Wnt/β-catenin expression. These findings suggest that TIPE3 is significantly elevated in patients with NSCLC and that downregulation of TIPE3 can suppress the malignant progression of NSCLC, which could serve as a potential diagnostic and treatment strategy for NSCLC.

Section snippetsBackground

Lung cancer is a malignant cancer with a high prevalence in the world, and it is the main type of cancer-related death [1]. The incidence of lung cancer has increased substantially, which has been located in the first male tumors [2]. Non-small cell lung cancer (NSCLC) being the most prevalent type, accounting for up to 85% of all lung cancer cases [3]. The overall cure and survival rates of NSCLC remain low, particularly in patients with metastasis, with a 5-year survival rate of less than 5%

Tumor Tissues and Clinical Ethics

A total of 60 cancerous tissues and paired adjacent noncancerous tissues from patients with NSCLC were collected in Cangzhou Central Hospital from January 2020 to December 2022. Of the 60 patients, 32 had metastases and 28 did not. All patients were pathologically diagnosed and tissues obtained during surgery were collected immediately and stored at -80 °C to prevent RNA loss. Written informed consent was obtained from each patient prior to sample collection. All the experiments were approved

TIPE3 is highly expressed in NSCLC tissues and cell lines

We analyzed the expression of TIPE3 in NSCLC tissues and compared it with that in para-tumor tissues. The results showed that TIPE3 was highly expressed in NSCLC tissues (Fig 1A). Furthermore, TIPE3 expression was higher in patients with metastasis than in those without metastasis (Fig 1B). The Kaplan–Meier plot revealed that high TIPE3 expression was associated with poor overall survival in patients with NSCLC (Fig 1C). Moreover, TIPE3 expression was detected in NSCLC cell lines, and compared

Discussion

Accumulating evidence has shown that TIPE3 plays a crucial role in various biological processes, particularly in the initiation, progression, and metastasis of cancer. To date, the expression patterns and biological functions of TIPE3 in NSCLC have been documented, leading to its recognition as a diagnostic biomarker and therapeutic target for NSCLC [9]; however, the role of TIPE3 and the regulatory pathway it participates in NSCLC remain largely unknown. NSCLC remains the most common type of

Ethics approval and consent to participate

All the experiments were approved by the Ethics Committee of Cangzhou Central Hospital (approval code 2021-167-02(z)). Written informed consent was obtained from each patient prior to sample collection. The procedures involving human subjects were conducted following the Declaration of Helsinki. The experimental and animal care procedures were conformed to the Guide for the Care and Use of Laboratory Animals produced by the National Institutes of Health. The experimental procedures were in

Consent for publication

Not applicable.

Availability of data and materials

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Funding

Not applicable.

Declaration of Competing Interest

☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhenfeng Zong reports was provided by Cangzhou Central Hospital. Zhenfeng Zong reports a relationship with Cangzhou Central Hospital that includes: employment. Zhenfeng Zong has patent

References (29)WoodD.E. et al.Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology

J Natl Compr Canc Netw

(2018)

NitureS. et al.TNFAIP8: Inflammation, Immunity and Human Diseases

J Cell Immunol

(2019)

ZhangL. et al.Tumor Necrosis Factor-α Induced Protein 8: Pathophysiology, Clinical Significance, and Regulatory Mechanism

Int J Biol Sci

(2018)

TianZ. et al.TNFAIP8 family gene expressions in the mouse tail intervertebral disc injury model

JOR Spine

(2020)

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