Highlights
- •Down-regulated miR-340 could suppress SCC cell proliferation, migration and invasion.
- •RhoA expression is negatively correlated with miR-340 level in SCC tissues.
- •RhoA is a novel direct target of miR-340 in SCC cells.
- •miR-340 suppresses the proliferation, migration and invasion of SCC through directly inhibiting RhoA/ROCK/MYPT1 and RhoA/ROCK/ERK1/2 pathways.
Abstract
Background
MicroRNAs are reported to play an important role in tumor growth and metastasis, including
squamous cell carcinoma (SCC). Accumulative evidence has revealed that dysregulated
miR-340 expression contributed to the carcinogenesis and development of various cancers.
Objective
The aim of the current study was to investigate the role and the underlying mechanism
of miR-340 in SCC cell proliferation, migration and invasion.
Methods
Quantitative real-time PCR was performed to examine the expression of miR-340 in SCC
tissues and cell lines. The function of miR-340 in SCC was investigated through Cell
Counting Kit-8, wound healing, transwell migration and invasion assays. Bioinformatics
analysis, luciferase reporter assay, western blotting and immunohistochemical analysis
were conducted to predict and confirm the target gene of miR-340.
Results
In the present study, we first found that miR-340 was significantly decreased in both
SCC tissues and cell lines. Moreover, ectopic expression of miR-340 remarkably attenuated
SCC cell proliferation, migration and invasion, whereas inhibition of endogenous miR-340
promoted SCC cell proliferation, migration and invasion in vitro. Our subsequent bioinformatics
analysis and luciferase reporter assay showed that RhoA was a novel direct target
of miR-340 in SCC cells, and the knockdown of RhoA expression rescued the effects
of miR-340 inhibition on SCC cell proliferation, migration and invasion. More importantly,
the expression of RhoA and miR-340 was negatively correlated in SCC tissues.
Conclusion
Our findings demonstrate the tumor suppressor role of miR-340 in SCC by directly regulating
RhoA. Therefore, restoration of miR-340 expression can be a potential therapeutic
approach for SCC treatment.
Abbreviations:
CCK-8 (Cell Counting Kit-8), qRT-PCR (quantitative real-time PCR), 3′UTR3′ (untranslated region), ESC (Cesophageal squamous cell carcinoma), MiRNAs (microRNAs), MYPT1 (protein phosphatase 1 regulatory subunit 12A), NHEK (normal human epidermal keratinocyte), OSC (Coral squamous cell carcinoma), OTR (organ transplant recipients), ROCK (Rho-associated kinases), SCC (squamous cell carcinoma)Keywords
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Article Info
Publication History
Published online: September 11, 2018
Accepted:
September 4,
2018
Received in revised form:
August 23,
2018
Received:
April 10,
2018
Identification
Copyright
© 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
