miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker

Abstract

Background

MicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC).

Methods

In this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo.

Results

We found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC.

Conclusion

These findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.