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FAM83B regulates mitochondrial metabolism and anti-apoptotic activity in pulmonary adenocarcinoma

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Abstract

Chemotherapy is an effective therapeutic modality; nevertheless, a significant proportion of patients diagnosed with lung adenocarcinoma (LUAD) demonstrate resistance to chemotherapy. Therefore, it is crucial to understand the potential regulatory mechanisms to develop novel treatment strategies. This study aims to understand how increased FAM83B expression impacts mitochondrial activity, cell apoptosis, and chemotherapy effectiveness in LUAD. Multiple assays, such as CCK8, wound healing, EdU, and transwell assays, were employed to confirm the augmented chemotherapy resistance, heightened cell proliferation, migration, and invasion caused by FAM83B overexpression in LUAD cells. Furthermore, MIMP, MTG, and ATP assays were utilized to quantify changes in mitochondrial metabolism. In vitro functional assays were performed to evaluate the influence of FAM83B overexpression on the malignant progression and resistance mechanisms to chemotherapy in LUAD. In the context of this study, it was determined that LUAD patients with increased FAM83B expression had shorter survival times, and tissue samples with FAM83B overexpression were more prone to metastasis compared to primary samples. As a result, FAM83B is identified as an adverse prognostic marker. The mechanistic analysis demonstrated that FAM83B impedes the translocation of calbindin 2 (CALB2) from the cytoplasm to the mitochondria, resulting in the inhibition of apoptosis and the promotion of mitochondrial activity. Consequently, this ultimately confers resistance to chemotherapy in LUAD. Furthermore, the administration of metformin, which blocks mitochondrial oxidative phosphorylation (OXPHOS), can restore sensitivity to drug resistance in LUAD. Taken together, these findings provide substantial evidence supporting the notion that FAM83B enhances chemotherapy resistance in LUAD through the upregulation of mitochondrial metabolism and the inhibition of apoptosis.

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Funding

This research was supported by the National Natural Science Foundation of China (NSFC, grant no. 81402181) and the National Natural Science Foundation of Shandong Province (grant no. ZR2023MH105).

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Authors and Affiliations

  1. Department of Pathology, School of Basic Medical Sciences and QiLu Hospital, Shandong University, Jinan, 250012, Shandong, China

    Jiajia Wang, Panpan Li, Jing Zhang, Ke Yue, Yan Wang & Xiaojuan Wu

  2. Department of Orthopedics, Shandong Provincial Third Hospital, Jinan, 250031, Shandong, China

    Limin Sun

Authors
  1. Jiajia Wang
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  2. Panpan Li
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  3. Limin Sun
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  4. Jing Zhang
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  5. Ke Yue
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  6. Yan Wang
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  7. Xiaojuan Wu
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Contributions

The study was conceptualized by X. W. and the manuscript was revised by her. J. W. edited the manuscript and prepared Figs. 2, 3 and 5. J. Z. and Y. W. performed the IHC assays. P. L. and L. S. carried out Figs. 1 and 4. K. Y. prepared Fig. 6. All authors reviewed the manuscript.

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Correspondence to Xiaojuan Wu.

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The authors declare no conflicts of interest related to this work.

Ethical Statement

These procedures were performed in accordance with the ethical standards of the Committee on Human Experimentation of Shandong University Medical Research Ethics Committee.

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Wang, J., Li, P., Sun, L. et al. FAM83B regulates mitochondrial metabolism and anti-apoptotic activity in pulmonary adenocarcinoma. Apoptosis (2024). https://doi.org/10.1007/s10495-024-01944-7

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