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TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway

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Abstract

The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. This study explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.

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Data Availability

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

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Funding

This work was supported by the key research and development projects of Gansu Province (Grant No. 17YF1FA126). Special fund project for doctoral training program of Lanzhou University Second Hospital (Grant No.YJS-BD-25). Cui Ying Science and Technology Innovation plan project of Lanzhou University Second Hospital (Grant No. CY2017-BJ05). Innovative Development Program for Medical Graduate students (Grant No. Izuyxcx-2022-106). Authors Yang He and Bin Zhang have received research support from Panfeng Shang.

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  1. Yang He and Bin Zhang contributed equally to this work and are considered to be co-first authors.

Authors and Affiliations

  1. Lanzhou University, Lanzhou, Gansu, China

    Yang He, Bin Zhang, Dali Han, Yuelin Du, Xingxing Zhang & Hongbo Wang

  2. Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, The Second Clinical Medical College of Lanzhou University, No.82 Cui Ying Gate, Cheng Guan District, Lanzhou, Gansu, China

    Zhongjin Yue & Panfeng Shang

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  1. Yang He
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by [YH], [BZ], and [DH]. The first draft of the manuscript was written by [YD], [XZ], and [HW]. [ZY] designed the concept and experiments. The project was funded by [PS], and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Panfeng Shang.

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The authors declare no conflict of interest.

Ethical Approval

This study involving human participants was conducted in accordance with the ethical standards of the institutional and national research committee and the Helsinki Declaration 2013. This study was conducted by the Ethical Committee of the Lanzhou University Second Hospital (2022A-206).

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He, Y., Zhang, B., Han, D. et al. TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway. Biochem Genet 61, 1265–1281 (2023). https://doi.org/10.1007/s10528-022-10319-z

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