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

Abstract

PurposeAccumulating 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 MethodsmiR-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.ResultsmiR-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.ConclusionOur 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.

Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients

“…At present, several miRNAs are known to be useful in the early diagnosis of cancers, including miR-21[ 19 ], miR-486[ 20 ], miR-24[ 21 ], and miR-125a-5p[ 22 ]. In addition, miR-191[ 23 ], miR-1908[ 24 ], miR-200c[ 25 ], and miR-217[ 26 ] were found to be potential prognostic indictors in cancer. However, these studies only used a single indictor or a limited number of patients for survival analysis.…”

Bioinformatics-based analysis of the lncRNA–miRNA–mRNA and TF regulatory networks reveals functional genes in esophageal squamous cell carcinoma

“…A study found that the silencing of EGR1 reduced cisplatin-induced apoptosis in WHCO1 cells [ 62 ]. Additionally, Gao et al also reported that miR-191 could increase cell proliferation and invasion, which might reduce EGR1 expression by binding its 3′UTR involved in ESCC progression [ 63 ]. SOX2 was the first one identified, located at chromosome 3q26.33, as a 317 amino acid transcription factor containing an HMG domain, which involved in cell proliferation, apoptosis, differentiation and affects the prognosis of ESCC [ 64 ].…”

Upregulation of microRNA-191 can serve as an independent prognostic marker for poor survival in prostate cancer

“…[15] The prognostic value of miR-191 in various cancer types have also been investigated. For example, in the study by Gao et al, [22] Kaplan–Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of esophageal squamous cell carcinoma prognosis. Song et al [23] found that the expression of miR-191 closely associated with the tumor size, pTNM stage, lymph node metastasis and perineural invasion, and poor prognosis of pancreatic cancer.…”