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Iron metabolism protein transferrin receptor 1 involves in cervical cancer progression by affecting gene expression and alternative splicing in HeLa cells

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Abstract

Background

Transferrin receptor 1 (TfR1), encoded by TFRC, is a key regulator of iron homeostasis and plays important roles in many diseases, including cancers.

Objective

To decipher the underlying molecular functions of TfR1 based on its influence on transcriptome profile in cancer cells.

Methods

In this study, we first identified the expression pattern and prognostic influence of TFRC in cervical cancer patients from TCGA database. To explore the regulatory outcomes of TfR1 from the view of whole transcriptome profile, we generated TFRC knockdown (TFRC-KD) HeLa cells and negative control (NC) cells using short hairpin RNA (shRNA) method. Unbiased transcriptome sequencing (RNA-seq) experiment was used to analyze the global expression level and alternative splicing (AS) changes between TFRC-KD and NC cells.

Results

We found TFRC was consistently elevated in cervical cancer samples and tightly associated with prognosis of patients. Differential expression analysis revealed that 629 differentially expressed genes (DEGs) were identified between TFRC-KD and NC. Functional enrichment analysis of these DEGs revealed that TFRC-KD extensively disturbed cell physiology related pathways, including immunity, cell metabolism and gene expression. Moreover, dysregulated AS profile also indicated that TfR1 has important roles in the AS regulation. Hundreds of TfR1-regulated AS genes were involved in DNA repair, cell death, transcription and viral reproduction pathways, which were tightly associated with cancer cell progression.

Conclusions

In summary, we for the first time explored the molecular functions of TfR1 at transcriptional and post-transcriptional levels. These results demonstrate TfR1 participates in the progression of cervical cancer by affecting the expression and AS levels of genes in cancer associated pathways, which greatly extends our understanding of TfR1 functions besides iron homeostasis and provide novel options in cancer treatment by targeting TfR1.

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Acknowledgements

We thank members from ABLife Inc., Wuhan for their valuable assistance in data processing and analysis.

Funding

This study was supported by Natural Science Foundation of Hubei Province (2020CFB592).

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Authors and Affiliations

  1. Department of Allergy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China

    Nan Huang, Xiaolong Wang & Wenjing Li

  2. Center for Genome Analysis, ABLife Inc., Wuhan, People’s Republic of China

    Yaxun Wei, Qi Wang & Dong Chen

  3. Oncology Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

    Yi Cheng

  4. Science Department, Wuhan Ruixing Biotechnology Co. Ltd., Wuhan, People’s Republic of China

    Qi Wang & Dong Chen

Authors
  1. Nan Huang
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  2. Yaxun Wei
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  3. Yi Cheng
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  4. Xiaolong Wang
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  5. Qi Wang
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  6. Dong Chen
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  7. Wenjing Li
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Correspondence to Wenjing Li.

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This article does not contain any research involving humans or animals as subjects of research.

Online data deposition

The datasets obtained in the present study are available from the National Center for Biotechnology Information Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE131598.

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Huang, N., Wei, Y., Cheng, Y. et al. Iron metabolism protein transferrin receptor 1 involves in cervical cancer progression by affecting gene expression and alternative splicing in HeLa cells. Genes Genom 44, 637–650 (2022). https://doi.org/10.1007/s13258-021-01205-w

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  • DOI: https://doi.org/10.1007/s13258-021-01205-w

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