PS02.053: DUAL-STRANDS OF MIR-150-DUPLEX (MIR-150–5P AND MIR-150–3P) ACTED AS ANTI-TUMOR MIRNAS THROUGH TARGETING SPOCK1 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract

Abstract Background MicroRNAs (miRNAs) belong to a group of small non-coding RNA molecules that act as pivotal agents responsible for fine-tuning RNA expression in a sequence-dependent manner. A large number of studies showed that dysregulated miRNAs are deeply involved in the development of cancer cells, as well as their metastasis and drug resistance. Based on our original miRNA expression signatures by RNA-sequencing revealed that both strands of miR-150–5p (the guide strand) and miR-150–3p (the passenger strand) was downregulated in several cancers. The general concept of miRNA biogenesis posits that the passenger strand of miRNA (the minor strand or miRNA*) derived from duplex miRNA is degraded and does not regulate gene expression. Here, we aimed that to investigate functional significance of these miRNAs in esophageal squamous cell carcinoma (ESCC). Methods Cancer cell proliferation, migration and invasion abilities were performed by using mature miRNAs or siRNAs. Genome-wide gene expression analyses and in silico analyses were applied to identify miRNA target genes in ESCC cells. Results Expression levels of miR-150–5p and miR-150–3p were significantly reduced in ESCC clinical specimens and cell lines. Cancer cell aggressiveness was inhibited by ectopic expression of these miRNAs. A total of 12 genes were identified as oncogenic targets by both miR-150–5p and miR-150–3p in ESCC cells. SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was directly regulated by both miR-150–5p and miR-150–3p by luciferase reporter assay. Overexpression of SPOCK1 was detected in ESCC specimens and knockdown of SPOCK1 by siRNA significantly inhibited cancer cell migration and invasion abilities. Conclusion Both strands of miR-150-duplex (miR-150–5p and miR-150–3p) acted as anti-tumor miRNAs in ESCC. Overexpression of SPOCK1 was enhanced cancer cell aggressiveness. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept in cancer research. We suggest that identification of novel function of passenger strands of miRNAs and the RNA networks they regulate might enhance our understanding of the molecular pathogenesis of ESCC. Disclosure All authors have declared no conflicts of interest.