Exosomal miR-130b-3p Promotes Progression and Tubular Formation Through Targeting PTEN in Oral Squamous Cell Carcinoma.

Wei Yan,Yuping Wang,Yanjun Guo,Qiang Li,Yong Chen,Xiaotong Wei

doi:10.3389/fcell.2021.616306

Abstract

Oral squamous cell carcinoma (OSCC), accounting for two-thirds of head and neck cancer, is characterized by poor prognosis and a high rate of mortality. Exosomes have emerged as potential molecule-shuttle in intercellular communication, thereby regulating the physiological processes of recipient cells. To date, the effect of exosomal microRNAs (miRNAs) on the progression of OSCC has not been fully investigated. In this study, we found that the protein, but not mRNA expression of Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was decreased in OSCC. The results revealed that miR-130b-3p was an important negative regulator for PTEN expression. Additionally, overexpression and knockdown of miR-130b-3p enhanced and inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs), respectively. Also, miR-130b-3p was transferred by exosomes to HUVECs and then promoted angiogenesis and inhibit the expression of PTEN. Furthermore, exosomal miR-130b-3p derived from OSCC cells promoted tumor growth and blood vessel formation in the xenograft mice model. Taken together, we demonstrated that exosome-mediated miR-130b-3p promoted progression and tubular formation in OSCC in vitro and in vivo. These results would provide new insight into exploring biomarkers and effective therapeutic strategies for OSCC.

Highlights

Head and neck cancer (HNC) has emerged as a significant health issue worldwide, with over 450,000 new diagnosed patients per year (Torre et al, 2015), of which more than 95% of malignant tumors are squamous cell carcinomas, including oral squamous cell carcinoma (OSCC; Chinn and Myers, 2015)
The mRNA expression of PTEN did not display the difference between OSCC and control tissues (Figure 1C), indicating that posttranscription may play a role in the regulation of PTEN in OSCC
IHC assay was applied to assess the abundance of PTEN and the results showed that PTEN was significantly reduced in OSCC cells relative to control cells (Figure 1D)

Summary

Introduction

Head and neck cancer (HNC) has emerged as a significant health issue worldwide, with over 450,000 new diagnosed patients per year (Torre et al, 2015), of which more than 95% of malignant tumors are squamous cell carcinomas, including oral squamous cell carcinoma (OSCC; Chinn and Myers, 2015). Several biological essential molecules, including microRNAs (miRNAs), enzymes, long non-coding RNAs, are delivered via exosomes, thereby regulating cellular activities of recipient cells (Zhang et al, 2016). Increasing evidence has revealed that exosome-delivered molecules play an essential role in regulating cancer, including tumor development, progression, angiogenesis, recurrence, metastasis, and chemoresistance (Zhang et al, 2015). MiRNAs are a group of well-studied exosome-shuttled molecules in biological and pathological processes of various cancer types (Melo et al, 2014; Thind and Wilson, 2016)

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Conclusion