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Upregulation of FAM50A promotes cancer development

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Abstract

FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

GTEx:

Genotype-tissue expression database

TIMER:

Tumor immune estimation resource

GEPIA2:

Gene expression profiling interactive analysis 2

UALCAN:

University of Alabama at Birmingham Cancer Data Analysis Portal

TILs:

Tumor-infiltrating lymphocytes

TISIDB:

Tumor–immune system interactions database

KEGG:

Kyoto Encyclopedia of Genes and Genomes

GO:

Gene Ontology

BLCA:

Bladder urothelial carcinoma

BRCA:

Breast invasive carcinoma

CHOL:

Cholangiocarcinoma

COAD:

Colon adenocarcinoma

ESCA:

Esophageal carcinoma

HNSC:

Head and neck squamous cell carcinoma

KICH:

Kidney chromophobe

KIRC:

Kidney renal clear cell carcinoma

KIRP:

Kidney renal papillary cell carcinoma

LIHC:

Liver hepatocellular carcinoma

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

PRAD:

Prostate adenocarcinoma

READ:

Rectum adenocarcinoma

STAD:

Stomach adenocarcinoma

THCA:

Thyroid carcinoma

UCEC:

Uterine corpus endometrial carcinoma

DLBC:

Lymphoid neoplasm diffuse large B-cell lymphoma

PAAD:

Pancreatic adenocarcinoma

THYM:

Thymoma

CPTAC:

Clinical proteomic oncology analysis

OV:

Ovarian cancer

LUNG:

Lung cancer

GBM:

Glioblastoma multiforme

TGCT:

Testicular cancer

KIPAN:

Pan-kidney cohort

GBMLGG:

Lower grade glioma and glioma

COADREAD:

Colon adenocarcinoma

MSI:

Microsatellite instability

UCS:

Uterine carcinosarcoma

SKCM:

Skin cutaneous melanoma

UVM:

Uveal melanoma

WT:

Wilms tumor

DFS:

Disease-free survival

DSS:

Disease-specific survival

PFS:

Progression-free survival

LGG:

Brain lower grade glioma

SARC:

Sarcoma

RT-PCR:

Real-time polymerase chain reaction

HCC:

Hepatocellular carcinoma

siRNA:

Small interfering RNA

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Acknowledgements

We are grateful to all of those with whom we have had the pleasure to work during this and other related projects.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81972648, 82172915, and 81773011) and the Chongqing Medical University Program for Youth Innovation in Future Medicine (Grant Number W0084).

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Authors and Affiliations

  1. Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Mei-Zhen Hu, Zhi-Zheng Dai, Hong-Yu Ji & Kai-Fu Tang

  2. The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325015, People’s Republic of China

    An-Qi Zheng

  3. School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Hang Liang, Jun-Nan Liu, Shu-Juan Zhu & Ke-Jian Wang

  4. Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Choqing, 400016, People’s Republic of China

    Mei-Mei Shen

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Contributions

All authors contributed to the study conception and design. MZH, ZZD, HYJ, AQZ, HL, MMS, and JNL performed the experiments and analyzed the data. The first draft of the manuscript was written by MZH. KF Tang reviewed the manuscript. SJZ and KJW supervised the study. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Shu-Juan Zhu or Ke-Jian Wang.

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The authors have no relevant financial or nonfinancial interests to disclose.

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The Ethics Committee of ChongQing Medical University has confirmed that no ethical approval is required.

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Cite this article

Hu, MZ., Dai, ZZ., Ji, HY. et al. Upregulation of FAM50A promotes cancer development. Med Oncol 40, 217 (2023). https://doi.org/10.1007/s12032-023-02072-z

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