miR-19a may function as a biomarker of oral squamous cell carcinoma (OSCC) by regulating the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-09-14 DOI:10.1111/jop.13478
Jijun Chen, Liang Wang, Danhua Ma, He Zhang, Jiayan Fan, Hongyan Gao, Xinyu Xia, Wei Wu, Yuyuan Shi
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Abstract

Background

In this study, we aimed to investigate the potential of miR-19a as a biomarker of OSCC and its underlying molecular mechanisms.

Methods

We collected serum and saliva samples from 66 OSCC patients and 66 healthy control subjects. Real-time PCR analysis, bioinformatic analysis and luciferase assays were performed to establish a potential signaling pathway of miR-19a/GRK6/GPCRs/PKC. Flowcytometry and Transwell assays were performed to observe the changes in cell apoptosis, metastasis and invasion.

Results

We found that miR-19a, GPR39 mRNA and PKC mRNA were upregulated while GRK6 mRNA was downregulated in the serum and saliva samples collected from OSCC patients. Moreover, in silico analysis confirmed a potential binding site of miR-19a on the 3′UTR of GRK6 mRNA, and the subsequent luciferase assays confirmed the molecular binding between GRK6 and miR-19a. We further identified that the over-expression of miR-19a could regulate the signaling between GRK6, GPR39 and PKC via the signaling pathway of miR-19a/GRK6/GPR39/PKC, which accordingly resulted in suppressed cell apoptosis and promoted cell migration and invasion.

Conclusion

Collectively, the findings of our study propose that miR-19a is a crucial mediator in the advancement of OSCC, offering a potential avenue for the development of innovative therapeutic interventions aimed at regulating GRK6 and its downstream signaling pathways.

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miR-19a可能通过调节miR-19a/GRK6/ gpcr /PKC的信号通路,在中国人群中作为口腔鳞状细胞癌(OSCC)的生物标志物
在这项研究中,我们旨在研究miR-19a作为OSCC生物标志物的潜力及其潜在的分子机制。方法采集66例OSCC患者和66例健康对照者的血清和唾液样本。通过Real-time PCR分析、生物信息学分析和荧光素酶分析,建立miR-19a/GRK6/ gpcr /PKC的潜在信号通路。流式细胞术和Transwell法观察细胞凋亡、转移和侵袭的变化。结果我们发现,在OSCC患者的血清和唾液样本中,miR-19a、GPR39 mRNA和PKC mRNA表达上调,GRK6 mRNA表达下调。此外,硅分析证实了miR-19a在GRK6 mRNA的3'UTR上的潜在结合位点,随后的荧光素酶测定证实了GRK6与miR-19a之间的分子结合。我们进一步发现过表达miR-19a可以通过miR-19a/GRK6/GPR39/PKC信号通路调节GRK6、GPR39和PKC之间的信号通路,从而抑制细胞凋亡,促进细胞迁移和侵袭。总之,我们的研究结果表明,miR-19a是OSCC进展的关键介质,为开发旨在调节GRK6及其下游信号通路的创新治疗干预提供了潜在途径。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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