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HAPLN3 inhibits apoptosis and promotes EMT of clear cell renal cell carcinoma via ERK and Bcl-2 signal pathways

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Abstract

Hyaluronan and proteoglycan link protein 3 (HAPLN3) is a member of the hyaluronan and proteoglycan link protein family expressed in the extracellular matrix closely associated with the development and occurrence of various malignant tumors; yet, its function in clear cell renal cell cancer (ccRCC) is still poorly understood. The following study investigated the progress and mechanism of HAPLN3 on ccRCC using bioinformatics analysis and in vitro experiments. In order to determine whether HAPLN3 is differentially expressed in ccRCC, we analyzed data from the Cancer Genome Atlas (TCGA) and GSE40435 and further validated them in the Human Protein Atlas (HPA) database. Simultaneously, the TCGA dataset was utilized to study the relationship between HAPLN3 expression and the progression of ccRCC and its prognostic value in ccRCC. Gene enrichment analysis (GSEA) was used to explore HAPLN3-related signaling pathways in ccRCC. The TIMER database investigates the link for both HAPLN3 and immune cell infiltration. Different ccRCC cell lines the role of HAPLN3 on cell biological behavior in vitro. HAPLN3 was increased in ccRCC, and its high expression was related to the patients' survival rates and clinical characteristics. GSEA showed that HAPLN3 is mainly enriched in proliferative and metastatic pathways. In addition, HAPLN3 was an independently associated significant predictor in patients with ccRCC. Functional experiments demonstrated that HAPLN3 could promote the proliferation, migration, and invasion of ccRCC cells through the ERK1/2 signaling pathway. To sum up, our data suggest that HAPLN3 may serve as a new prognostic biomarker and potential therapeutic target for ccRCC.

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Acknowledgements

The results published in this study are from publicly available datasets, which are available in the TCGA database and the GEO database. This research was supported by the Natural Science Foundation of China (grant number 81860454) and Key Research and Development Program of Jiangxi Province (grant number 20203BBGL73180).

Funding

This research was supported by the Natural Science Foundation of China (grant number 81860454) and Key Research and Development Program of Jiangxi Province (grant number 20203BBGL73180).

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Author notes

  1. Yi Ding, Shida Xiong, and Xinpeng Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China

    Yi Ding, Shida Xiong, Xinpeng Chen, Qiufeng Pan, Jiawen Fan & Ju Guo

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  1. Yi Ding
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  2. Shida Xiong
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  3. Xinpeng Chen
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  4. Qiufeng Pan
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  5. Jiawen Fan
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Contributions

JG and YD: study design. YD, QP, SX, HH, and XC: data collection and analysis. YD and XC: performed the experiments. All authors contributed to data interpretation and the writing and review of this manuscript.

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Correspondence to Ju Guo.

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The authors have declared that no competing interest exists.

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All procedures in this study were conducted in accordance with the First Affiliated Hospital Ethics Committee of Nanchang University. This article does not contain any studies with animal subjects.

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Ding, Y., Xiong, S., Chen, X. et al. HAPLN3 inhibits apoptosis and promotes EMT of clear cell renal cell carcinoma via ERK and Bcl-2 signal pathways. J Cancer Res Clin Oncol 149, 79–90 (2023). https://doi.org/10.1007/s00432-022-04421-3

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  • DOI: https://doi.org/10.1007/s00432-022-04421-3

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