Objective: Micro RNA (miR)-363 has many important biological functions in cancers, but its roles in esophageal squamous cell carcinoma (ESCC) remain unclear.
Methods: We used reverse transcription PCR to quantify the expression of miR-363 in 80 ESCC tissues and analyzed its relationship with clinicopathological factors and overall survival. The effects of miR-363 on cell proliferation, apoptosis, and invasion were detected using the MTT assay, flow cytometry, and Transwell invasion assays, respectively. Further, we investigated the post-transcriptional regulation of sperm-associated antigen 5 (SPAG5) expression by miR-363 using luciferase reporter assays. Finally, the effects of SPAG5 on miR-363 were studied by SPAG5 overexpression.
Results: miR-363 expression was decreased in both ESCC specimens and cell lines, compared with controls, and correlated with lymph node metastasis and tumor differentiation. Low miR-363 expression was identified as an independent prognostic factor for ESCC. miR-363 overexpression decreased ESCC cell proliferation and invasion and increased apoptosis, while the opposite was seen after miR-363 inhibition. Moreover, SPAG5 was identified as a direct target of miR-363, and the reintroduction of SPAG5 restored miR-363-induced effects.
Conclusions: miR-363 acts as a tumor suppressor by post-transcriptionally regulating SPAG5 expression, suggesting its potential as a diagnostic biomarker and therapeutic target for ESCC.
Keywords: Micro RNA-363; biomarker; esophageal squamous cell carcinoma; sperm-associated antigen 5; therapeutic target; tumor suppressor.