Mir-208 promotes cell proliferation by repressing SOX6 expression in human esophageal squamous cell carcinoma

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancer in developing countries. The prognosis and survival rate of ESCC are very poor. Recently, microRNAs (miRNAs) have emerged as important regulators of cancer cell biological processes. To better understanding the molecular mechanisms by which they regulate the behavior of cancer cells is needed.MethodsThe expression of miR-208 was examined in ESCC cell lines and tumor tissues by real-time PCR. Proliferation capability of ESCC cells upon regulation of miR-208 expression was detected by MTT assay, colony formation assay, anchorage-independent growth ability assay and flow cytometry analysis. The target of miR-208 was determined by western blotting analysis, luciferase reporter assay and real-time PCR.ResultsmiR-208 was upregulated in ESCC cell lines and tissues. Overexpression of miR-208 in ESCC cells increased cell proliferation, tumorigenicity and cell cycle progression, whereas inhibition of miR-208 reduced cells proliferation, tumorigenicity and cell cycle progression. Additionally, SOX6 was identified as a direct target of miR-208. Ectopic expression of miR-208 led to downregulation of SOX6 protein, which resulted in the downregulation of p21, upregulation of cyclin D1 and phosphorylation of Rb.ConclusionsThese results suggest that miR-208 represents a potential onco-miR and participates in ESCC carcinogenesis by suppressing SOX6 expression.

MicroRNA-374a promotes esophageal cancer cell proliferation via Axin2 suppression

“…Cyclin D1 was inversely associated with Axin level in the lung cancer cell line (32), and β-catenin regulated the expression of cyclin D1 in colon carcinoma cells (33). Cyclin D1 expression and phosphorylation of Rb were also increased by another miRNA, miR-208, which promoted cell proliferation when ectopically expressed in esophageal squamous cell carcinoma lines (22). Thus, the increased expression of cyclin D1 and phosphorylation of Rb by miR374a provided a further mechanism for the tumor-promotive effect of miR-374a.…”

“…The number of colonies was counted at the 5th day after seeding. The trypsinized cells were also seeded for an anchorage-independent growth ability assay as previously described (22). One thousand cells were suspended in 2 ml complete medium plus 0.33% agar.…”

“…Flow cytometric analysis was performed as previously described (22). The cells were harvested by trypsinization, washed in ice-cold PBS, and fixed in 80% ice-cold ethanol.…”

Curcumin inhibits growth of prostate carcinoma via miR-208-mediated CDKN1A activation

“…The abnormal expression of miRNAs has been detected in a number of tumors and contributed to tumor initiation and progression. Specifically, miR-208 has been rarely studied in cancers [33,34], whereas a role of miR-208 in PC has not been reported.…”

Differential expression of micrornas in medulloblastoma and the potential functional consequences

“…Liu et al (13) reported that hsa-miR208a induced epithelial cells converted to mesenchymal cells, promoted the pancreatic cancer cell metastasis and invasion, the overexpression was concerned with the activation of AKT/GSK-3β/snail signaling pathway. Li et al (12) have reported that hsa-miR-208a promoted the proliferation of human esophageal squamous cell carcinoma by inhibiting the expression of SOX6. Chen et al (1) have reported that hsamiR-1207-5p inhibited the growth of gastric cancer cells by acting on telomerase reverse transcriptase.…”