Abstract
Cancer related inflammation (CRI) plays an important role in the development of esophageal cancer (EC), and the target gene analysis shows that miR-302b potential target genes closely correlated to CRI important signaling pathways. The present study was to evaluate the inhibition of miR-302b on CRI in EC and its mechanism. We found that the expression levels of miR-302b in EC cells were lower than that in Het-1A cells, while TE11 with the lowest expression and OE33 with the highest. Inflammatory stimuli at 48 h significantly reduced expression of miR-302b in EC cells, but had no effect in Het-1A. After up-regulation of miR-302b in TE11 and down-regulation of miR-302b in OE33, it was found that miR-302b reduced CRI key transcription factors and representative cytokines. Then, over-expressed of miR-302b significantly altered potential target genes protein expressions and there was a negative correlation between miR-302b and potential target genes protein expressions (ERBB4, IRF2 and CXCR4) in EC tissues. Then reporter gene analysis revealed that miR-302b post-transcriptionally regulated expression of target genes by specific area of 3′-UTR. Transfected by target genes shRNA plasmids together could get the same effects of miR-302b on protein expression of CRI key transcription factors. Furthermore, miR-302b was able to repress tumor growth and transcription factors protein expression in vivo. These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC.
Highlights
Esophageal cancer (EC) is the eighth most common cancer worldwide, and the sixth most common cause of death from cancer [1]
We found that ERBB4, IRF2 or CXCR4 has cross-talk with HIF-1α, STAT3, and NFκB respectively [11,12,13]
To explore the role of miR-302b in esophageal cancer (EC), we analyzed the expression of miR-302b in 4 EC cell lines by RT-PCR
Summary
Esophageal cancer (EC) is the eighth most common cancer worldwide, and the sixth most common cause of death from cancer [1]. Despite a myriad of improvements in both diagnostic and therapeutic techniques over the past three decades, EC still has a poor prognosis, meaning that EC is a major public health problem in China [3]. It calls for more and more research on the molecular mechanisms responsible for EC carcinogenesis and development. Investigations have revealed the www.impactjournals.com/oncotarget key mediators of CRI, including transcription factors, chemokines, cytokines, and so on. These mediators show important value in diagnosis, treatment, and prognosis in different types of cancer. The regulation mechanisms of CRI in EC are unclear [5]
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