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Cancer-Associated Fibroblasts Boost Tumorigenesis of Clear Cell Renal Cell Carcinoma via Exosome-Mediated Paracrine SNHG1

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Abstract

Despite the dominant roles of cancer-associated fibroblasts (CAFs) have attached much attention in tumorigenesis, the CAFs-derived molecular determinants that regulate renal cell carcinoma (RCC) development remains elusive. Our previous study uncovered an oncogenic SNHG1 in the immune escape of RCC, whereas CAFs-derived exosomes could be a source accounting for increasing SNHG1 in RCC cells, this is still a mystery. The obtained CAFs and normal fibroblast (NFs) from fresh RCC and adjacent tissues were firstly identified using western blot and immunofluorescent staining. The enrichment of SNHG1 was validated by RT-qPCR. CAFs-derived exosomes were isolated from conditioned medium using ultracentrifugation method and ExoQuick-TC system. The internalization of exosomes, transfer of SNHG1, was measured by immunofluorescence. Regulation of conditioned medium or exosomal SNHG1 from CAFs on RCC biological functions was evaluated by CCK-8, EdU incorporation, colony formation, and transwell assays to assess the RCC cell proliferation, migration, and invasion. SNHG1 was significantly upregulated in CAFs isolated from RCC stroma. Exosomes derived from CAFs transferred SNHG1 to RCC cells and resulted in an increased SNHG1 expression in RCC cells. The exosomes excreted by CAFs promoted RCC cell proliferation, migration, and invasion, whereas the promotion effect of CAFs-exosomes on RCC progression was attenuated by SNHG1 knockdown. The present study revealed a new mechanism of exosomal SNHG1 extracted from CAFs enhanced RCC progression and may provide a potential target for the treatment of RCC.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Abbreviations

ANOVA:

One-way analysis of variance

CAFs:

Tumor-associated fibroblasts

ccRCC:

Clear cell RCC

FBS:

Fetal bovine serum

IHC:

Immunohistochemistry

lncRNAs:

Long-noncoding RNAs

NAT:

Nanoparticle tracking analysis

NFs:

Normal fibroblasts

PFA:

Paraformaldehyde

PBS:

Phosphate-buffered saline

RCC:

Renal cell carcinoma

RT-qPCR:

Real-time polymerase chain reaction

TEM:

Transmission electron microscope

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Acknowledgements

The authors would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by the Fund program: Henan provincial Medical Science and Technology Research Project (LHGJ20220192, LHGJ20220193) and Henan provincial Science and Technology Research Project (222102310629).

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Authors and Affiliations

  1. Department of Urology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, People’s Republic of China

    Pei Tian, Jing Li, Junkai Ren & Chaohong He

  2. Department of Urology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People’s Republic of China

    Jinxing Wei

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  1. Pei Tian
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  2. Jinxing Wei
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  3. Jing Li
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  4. Junkai Ren
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  5. Chaohong He
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Contributions

CH: Conception and design of study. PT, JL: Acquisition of data. JW, JR: Analysis and interpretation of data. PT, JW: Drafting the manuscript. CH: Revising the manuscript critically for important intellectual content.

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Correspondence to Chaohong He.

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The authors declare that they have no conflicts of interest.

Ethical Approval

The study was approved by the Ethics Committees of the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital and the patient’s written informed consent.

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All participants were informed and gave written consent.

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Tian, P., Wei, J., Li, J. et al. Cancer-Associated Fibroblasts Boost Tumorigenesis of Clear Cell Renal Cell Carcinoma via Exosome-Mediated Paracrine SNHG1. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10512-8

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