Abstract
Evidence has shown that hypoxia promotes esophageal squamous cell carcinoma (ESCC) growth and metastasis, but the molecular mechanisms underlying that response remain poorly understood. MicroRNAs (miRNAs) are post-transcriptional regulators that participate in various cancer-related processes. Here, we demonstrated that hypoxia along with hypoxia-inducible factor 1α significantly increased expression of miR-10b-3p. Inhibition of miR-10b-3p weakened the effects of hypoxia on ESCC cell proliferation, migration and invasion, while miR-10b-3p overexpression had the opposite effects. Mechanistically, miR-10b-3p acted as cancer-promoting gene by targeting testis specific 10. Using a xenograft model, we observed that administration of miR-10b-3p agomir to tumors enhanced their growth and metastasis in vivo. These findings verified the potent regulatory role played by hypoxia-induced miR-10b-3p expression in ESCC progression. These results suggest that miR-10b-3p may be a useful therapeutic target for treating ESCC.
Highlights
Esophageal cancer has a poor prognosis and is a major cause of cancer-related mortality due to its high metastatic potential [1]
These data suggest that hypoxia increases miR-10b-3p expression through hypoxia-inducible factor 1α (HIF-1α) in esophageal squamous cell carcinoma (ESCC) cells
MiR-145 and miR-133b, reportedly interact with fascin homolog 1 or actin-bundling protein, which leads to enhancement of cell growth and invasion in ESCC [15, 16]
Summary
Esophageal cancer has a poor prognosis and is a major cause of cancer-related mortality due to its high metastatic potential [1]. Esophageal adenocarcinoma predominates in the western world, the majority of esophageal cancers in Asian countries are diagnosed as esophageal squamous cell carcinoma (ESCC) [2]. By suppressing the expression of their target genes, miRNAs can promote www.aging-us.com or inhibit both carcinogenesis and cancer progression [6]. MicroRNA-10b-3p affects prognosis and the response to neo-adjuvant therapy in pancreatic ductal adenocarcinoma [10] and is predictive of survival in hepatocellular carcinoma patients treated with sorafenib [11]. We examined the actions of miR-10b-3p in ESCC cells. Our findings suggest that hypoxia and hypoxia-inducible factor 1α (HIF-1α) enhance miR-10b-3p expression, which mediates ESCC cell growth by targeting testis specific 10 (TSGA10)
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