STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells

Abstract

AbstractsBackgroundEsophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet.MethodsFirstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo.ResultsDual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells.ConclusionCollectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.

miR-124 radiosensitizes human esophageal cancer cell TE-1 by targeting CDK4

“…This is consistent with a report by Zhang et al (2014c) who illustrated that miR-124 could increase the radiosensitivity of conditionally reprogrammed cells by blocking the expression of paired related homeobox 1 (PRRX1). It has also been shown that miR-124 expression is consistently suppressed in esophageal cancer tissues and cell lines, where it functions as a tumor suppressor (Cheng et al, 2015). Similar to their results, we found that the expression of miR-124 was downregulated in esophageal cancer tissues.…”

Constitutive activation of Pim1 kinase is a therapeutic target for adult T-cell leukemia

“…We also found that restoring miR-124a expression in ATL cells significantly decreases in vitro cellular proliferation and causes a significant reduction in tumor formation in vivo. Although miR-124 inhibition of STAT3 has been shown, 34 to our knowledge, this is the first study reporting miR-124a regulation of STAT3 in human leukemia/ lymphomas. Using a cancer profiler array along with in silico promoter analyses of genes downregulated by miR-124a, we identified STAT3 as a common regulator.…”

The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

“…Previous studies have suggested that lncRNAs serve as competing endogenous RNAs (ceRNAs) to sponge miRNAs, thereby regulating gene expression [19]. According to previous studies, miR-124 plays a suppressive role in cancers [20]. The role of miR-124 in bladder cancer was reported [21].…”