MicroRNA‑21 regulates the biological behavior of esophageal squamous cell carcinoma by targeting RASA1

Chen,Xiaohua; Cai,Sina; Li,Baoxia; Zhang,Xiaona; Li,Wenhui; Liang,Henglun; Cao,Xiaolong; Wang,Liping; Wu,Ziqing

doi:10.3892/or.2018.6944

MicroRNA‑21 regulates the biological behavior of esophageal squamous cell carcinoma by targeting RASA1

Authors:
- Xiaohua Chen
- Sina Cai
- Baoxia Li
- Xiaona Zhang
- Wenhui Li
- Henglun Liang
- Xiaolong Cao
- Liping Wang
- Ziqing Wu
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Affiliations: Department of Oncology, Panyu Central Hospital, Cancer Institute of Panyu, Guangzhou, Guangdong 511400, P.R. China, Department of Oncology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, State Laboratory of Oncology in South China, Sun Yat‑Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China, Graceland Medical Center, The Sixth Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Clinical Oncology, The First City Hospital of Chenzhou, Chenzhou, Hunan 423099, P.R. China, Department of Pathology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510310, P.R. China
Published online on: December 19, 2018 https://doi.org/10.3892/or.2018.6944
Pages: 1627-1637
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA‑21 (miR‑21) has been revealed to play a crucial role in regulating the biological behavior, including proliferation, migration, invasion and metastasis in certain cancers. However, its role in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. Based on the data of GSE13937 downloaded from Gene Expression Omnibus (GEO) database, miR‑21 was revealed to be one of the top 20 differentially expressed (DE) miRNAs screened using the Morpheus online tool. RAS p21 protein activator 1 (RASA1) was predicted as the target gene of miR‑21 using the predicting software and was combined with miR‑21 using the luciferase reporter assay. Its relative expression was significantly decreased, however, miR‑21 was increased in the tumor tissues compared to the normal adjacent tissues in patients with ESCC as determined by quantitative polymerase chain reaction (q‑PCR). Furthermore, overexpression of miR‑21 (mimic) could significantly decrease the gene level of RASA1. Conversely, downregulation of miR‑21 (inhibitor) significantly increased the gene level of RASA1, while downregulation of RASA1 (siRASA1) markedly increased the gene expression of miR‑21. Notably, the expression of Snail and vimentin were significantly increased by upregulation of miR‑21 and downregulation of RASA1. Transwell results revealed that miR‑21 and RASA1 regulated proliferation, migration and invasion in ESCC cells. In an in vivo model, miR‑21 inhibitor (antagomir) could inhibit tumor growth. In conclusion, miR‑21 regulated cell proliferation, migration, invasion and tumor growth of ESCC by directly targeting RASA1, which may have been achieved via regulation of Snail and vimentin. Anti‑miR‑21 revealed an antitumor effect. Thus, it may be considered as a possible target for ESCC therapy.

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