Abstract
Accumulating evidences indicate that microRNAs (miRNAs) play vital roles in multiple diseases, including cancer. In the present study, we showed that miR-6775-3p plays a tumor suppressive role in esophageal squamous cell carcinoma (ESCC). High expression miR-6775-3p is associated with good clinical outcomes of ESCC patients. Over-expression of miR-6775-3p inhibited tumor growth and liver metastasis of ESCC xenograft tumors. Enforced expression of miR-6775-3p inhibited ESCC cell proliferation, migration, and invasion. KEGG pathway analysis revealed that miR-6775-3p was associated with the genes on “pathway in cancer”. Mechanically, miR-6775-3p inhibited the expression of tumor antigens MAGE-A family through direct binding the 3′UTR region of MAGE-A mRNAs, and attenuated MAGE-A-inhibited transcriptional activity of tumor suppressor p53. In addition, miR-6775-3p also directly inhibits its host gene SLC7A5 which has been reported to play oncogenic roles in cancer progression. Interestingly, miR-6775-3p and its host gene SLC7A5 were directly transcriptionally induced by p53. Thus, for the first time, our study proposed a novel positive feedback regulation between miR-6775-3p and p53 via MAGE-A family, which plays crucial role in ESCC progression.
Highlights
As a common malignant tumor, esophageal cancer ranks sixth in the cause of cancer-relevant death all over the world[1]
Our results showed that miR-6775-3p expression was negatively associated with the histological grade, tumor infiltration, lymph node metastasis, distant metastasis or recurrence of Esophageal squamous cell carcinoma (ESCC) patients (Supplementary Table S2)
The results showed that the miR-6775-3p-transfected nude mice formed fewer liver metastasis colonies than those treated with the control miRNA (Fig. 1i, j)
Summary
As a common malignant tumor, esophageal cancer ranks sixth in the cause of cancer-relevant death all over the world[1]. Esophageal squamous cell carcinoma (ESCC) is the main histopathological type of esophageal cancer[2]. MicroRNAs (miRNAs) are a type of endogenous ncRNAs that modulate gene expression through inhibiting translation or cleaving RNA transcripts by a sequencespecific way[5,6]. It is well established that miRNAs involve in almost all physiological and pathological processes, and play crucial role in cancer progression[7,8,9]. Aberrant miRNA expression was observed in human cancers, with evidence for a causative role in tumorigenesis[10,11]. There are about half of miRNA genes locate among independent transcription units, while the intragenic miRNAs are embedded within intronic regions and oriented on the same DNA strand of host genes[12]
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