Yonsei Med J.  2017 Nov;58(6):1101-1110. 10.3349/ymj.2017.58.6.1101.

Overexpression of miR-191 Predicts Poor Prognosis and Promotes Proliferation and Invasion in Esophageal Squamous Cell Carcinoma

Affiliations
  • 1Department of Cardiac Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2Department of Cardiothoracic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
  • 3Department of Internal Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, China. 1347240737@qq.com

Abstract

PURPOSE
Accumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC).
MATERIALS AND METHODS
miR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191.
RESULTS
miR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion.
CONCLUSION
Our findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.

Keyword

miR-191; esophageal squamous cell carcinoma; early growth response 1; prognosis; proliferation; invasion

MeSH Terms

3' Untranslated Regions
Carcinoma, Squamous Cell/genetics/metabolism/*pathology
Cell Line, Tumor
*Cell Movement
Cell Proliferation
Esophageal Neoplasms/genetics/metabolism/*pathology
*Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
MicroRNAs/*genetics/metabolism
Middle Aged
Neoplasm Invasiveness/*genetics
Prognosis
RNA, Small Interfering
Real-Time Polymerase Chain Reaction
3' Untranslated Regions
MicroRNAs
RNA, Small Interfering
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