Tumor-Suppressive Function of miR-139-5p in Esophageal Squamous Cell Carcinoma

Abstract

Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

MicroRNA profiling in clear cell renal cell carcinoma tissues potentially links tumorigenesis and recurrence with obesity

“…However, miR-139-5p was not selected for validation. In other studies, it was consistently downregulated in ccRCC metastatic samples and oesophageal squamous cell carcinoma tissues obtained from patients with lymph node metastasis (Wu et al , 2012; Liu et al , 2013). miR-139-5p was also found to be associated with ccRCC survival in some studies but not all (Osanto et al , 2012; Wu et al , 2012).…”

Targeted deletion of miR‐139‐5p activates MAPK, NF‐κB and STAT3 signaling and promotes intestinal inflammation and colorectal cancer

“…An increasing number of studies focusing on miR‐139‐5p have been published in recent years, which indicate that miR‐139‐5p is closely correlated to human cancers by affecting various biological functions . Our previous studies provided evidence that miR‐139‐5p was down‐regulated in human CRC samples, and is associated with tumor staging .…”

“… also clarified the function of miR‐139‐5p as a tumor inhibitor by inducing apoptosis and causing cell cycle arrest in G0/G1 phase through targeting NOTCH1. Other studies have determined the effects of miR‐139‐5p on proliferation and apoptosis in other types of cancer . In the present study, we also evaluated the influence of miR‐139‐5p depletion on proliferation and apoptosis in an AOM/DSS mouse model.…”

MicroRNA‑139 inhibits the proliferation, migration and invasion of gastric cancer cells by directly targeting ρ‑associated protein kinase 1

“…Shen et al (22) demonstrated that miR-139 expression was also downregulated in colorectal cancer tissues compared with that in adjacent non-tumorous tissues, and decreased miR-139 expression has also been associated with colorectal cancer progression and metastasis. Furthermore, in a study by Liu et al (23), miR-139 expression was demonstrated to be reduced in esophageal squamous cell carcinoma tissues, and this reduction was associated with lymph node metastasis. These findings indicate that increasing miR-139 expression may be useful in the prevention of cancer progression.…”