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01.12.2018 | Primary research | Ausgabe 1/2018 Open Access

Cancer Cell International 1/2018

MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway

Zeitschrift:
Cancer Cell International > Ausgabe 1/2018
Autoren:
Yuhuan Wang, Shuhua Zhang, Hejing Bao, Shukun Mu, Baishen Zhang, Hao Ma, Shudong Ma
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12935-018-0563-6) contains supplementary material, which is available to authorized users.

Abstract

Background

Abnormal microRNA expression is closely related to cancer occurrence and development. miR-365a-3p plays an oncogenic role in skin cancer, but its role in lung cancer remains unclear. In this study, we aimed to investigate its role and underlying molecular mechanisms in lung cancer.

Methods

Western blot and real-time quantitative PCR (qPCR) were used to detect the expression of miR-365a-3p in lung adenocarcinoma and lung cancer cell lines. The effects of miR-365a-3p on lung cancer cell proliferation, migration, and invasion were also explored in vitro. The potential miR-365a-3p that targets USP33 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis. miR-365a-3p acts as an oncogene by promoting lung carcinogenesis via the downregulation of the miR-365a/USP33/SLIT2/ROBO1 axis based on western blot analysis. Subcutaneous tumourigenesis further demonstrated that miR-365a-3p promotes tumour formation in vivo.

Results

miR-365a-3p was upregulated in lung adenocarcinoma and lung cancer cell lines. Overexpression of miR-365a-3p promoted and inhibition of miR-365a-3p suppressed the proliferation, migration, and invasion of lung cancer cells. We identified USP33 as the downstream target of miR-365a-3p and observed a negative correlation between miR-365a-3p and USP33 expression in lung adenocarcinoma patients. The miR-365/USP33/SLIT2/ROBO1 axis, a new mechanism, was reported to inhibit the invasion and metastasis of lung cancer. A nude mouse model of lung cancer further verified these findings.

Conclusions

In summary, miR-365a-3p acts as an oncogene by promoting lung carcinogenesis via the downregulation of the USP33/SLIT2/ROBO1 signalling pathway, making the miR-365/USP33/SLIT2/ROBO1 axis a new mechanism of lung cancer promotion and a novel therapeutic target for predicting prognosis and response to gene therapy.
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