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pmid:37365497

Analysis of mRNA-miRNA interaction network reveals the role of CAFs-derived exosomes in the immune regulation of oral squamous cell carcinoma.

Wei-Zhou Wang · Xue Cao · Li Bian · Yue Gao · Ming Yu · Yi-Ting Li · Jian-Guo Xu · Yang-Hao Wang · He-Feng Yang · Ding-Yun You · Yong-Wen He

BMC cancer · 2023 doi:10.1186/s12885-023-11028-5

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Analysis of mRNA-miRNA interaction network reveals the role of CAFs-derived exosomes in the immune regulation of oral squamous cell carcinoma.
doi
10.1186/s12885-023-11028-5
pmid
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Wei-Zhou Wang
[1]
Xue Cao
[2]
Li Bian
[3]
Yue Gao
[4]
Ming Yu
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Yi-Ting Li
[6]
Jian-Guo Xu
[7]
Yang-Hao Wang
[8]
He-Feng Yang
[9]
Ding-Yun You
[10]
Yong-Wen He
journal
BMC cancer
year
2023
abstract
BACKGROUND: Cancer-associated fibroblasts (CAFs) have significant tumor regulatory functions, and CAFs-derived exosomes (CAFs-Exo) released from CAFs play an important role in the progression of oral squamous cell carcinoma (OSCC). However, a lack of comprehensive molecular biological analysis leaves the regulatory mechanisms of CAFs-Exo in OSCC unclear. METHODS: We used platelet derived growth factor-BB (PDGF-BB) to induce the transformation of human oral mucosa fibroblast (hOMF) into CAFs, and extracted exosomes from the supernatant of CAFs and hOMF. We validated the effect of CAFs-Exo on tumor progression by exosomes co-culture with Cal-27 and tumor-forming in nude mice. The cellular and exosomal transcriptomes were sequenced, and immune regulatory genes were screened and validated using mRNA-miRNA interaction network analysis in combination with publicly available databases. RESULTS: The results showed that CAFs-Exo had a stronger ability to promote OSCC proliferation and was associated with immunosuppression. We discovered that the presence of immune-related genes in CAFs-Exo may regulate the expression of PIGR, CD81, UACA, and PTTG1IP in Cal-27 by analyzing CAFs-Exo sequencing data and publicly available TCGA data. This may account for the ability of CAFs-Exo to exert immunomodulation and promote OSCC proliferation. CONCLUSIONS: CAFs-Exo was found to be involved in tumor immune regulation through hsa-miR-139-5p, ACTR2 and EIF6, while PIGR, CD81, UACA and PTTG1IP may be potentially effective targets for the treatment of OSCC in the future.
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analysis. The target genes were validated by RT-qPCR in cells and tumors. Statistical analysis Th
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However, a lack of comprehensive molecular biological analysis leaves the regulatory mechanisms of CAFs-Exo in OSCC unclear.\nMETHODS: We used platelet derived growth factor-BB (PDGF-BB) to induce the transformation of human oral mucosa fibroblast (hOMF) into CAFs, and extracted exosomes from the supernatant of CAFs and hOMF. We validated the effect of CAFs-Exo on tumor progression by exosomes co-culture with Cal-27 and tumor-forming in nude mice. The cellular and exosomal transcriptomes were sequenced, and immune regulatory genes were screened and validated using mRNA-miRNA interaction network analysis in combination with publicly available databases.\nRESULTS: The results showed that CAFs-Exo had a stronger ability to promote OSCC proliferation and was associated with immunosuppression. 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