Abstract
MicroRNAs (miRNAs) are a large family of small, non-coding RNAs that play a pivotal role in tumorigenesis. miR‑34a, which is a member of the miR-34 family, is a downstream target of p53. Increasing evidence shows that miR-34a dysregulation may contribute to tumor development and progression in numerous cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanism of miR-34a in the regulation of ESCC cells need to be further elucidated because of the complex regulative network of miRNAs. The miR-34a expression in ESCC samples has been confirmed using quantitative reverse transcription polymerase chain reaction. The effects of miR-34a on cell migration and invasion were examined in ESCC cell lines using wound healing and Transwell assays, respectively. The effects of miR-34a on matrix metalloproteinase (MMP)-2 and-9 and fibronectin typeIII domain containing 3B (FNDC3B) expression levels were detected by luciferase reporter assays and western blot analysis. Quantitative polymerase chain reaction revealed that the miR‑34a expression is significantly downregulated in the ESCC tissues compared to that in the adjacent normal tissues. miR-34a overexpression was significantly suppressed migration and invasion in the ESCC cells and simultaneously inhibited the MMP-2, MMP-9 and FNDC3B expression levels by targeting the coding and 3'-untranslated regions, respectively. The findings indicated that microRNA‑34a suppresses cell migration and invasion by targeting MMP-2, MMP-9, and FNDC3B in ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors in China [1]
Our study demonstrates that matrix metalloproteinase-2 (MMP-2)/matrix metalloproteinase-9 (MMP-9)/fibronectin type III domain containing 3B (FNDC3B) is a direct downstream target of miR-34a, and miR-34a overexpression in the ESCC cells decreases both messenger RNAs (mRNAs) production and protein expression of matrix metalloproteinase (MMP)-2/MMP-9/FNDC3B. miR-34a suppressed tumor cell invasion and migration in ESCC by suppressing MMP-2 and MMP-9/FNDC3B expression levels
The miR-34a expression in the ESCC was confirmed by determining the miR-34a levels in the ESCC and normal esophageal tissues through qRT-polymerase chain reaction (PCR) using U6 as the internal control
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors in China [1]. Some advances have been made in the treatment of ESCC, including surgery, chemotherapy, radiation, or a combination of these options. The associated prognosis of ESCC patients is still not satisfactory. The five-year overall survival rate of ESCC patients after surgery is only approximately 14-22% [2,3,4]. Tumor invasion and metastasis are the major causes of the poor prognosis of ESCC patients [5,6]. Some oncogenic and tumor suppressive factors have been reported to be associated with ESCC progression. Exploring the detailed molecular mechanisms of ESCC cell progression, invasion, and metastasis will help improve disease diagnosis and therapy
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