Shrimp miRNA suppresses the stemness of human cancer stem cells via the PIN1 pathway

Abstract

A tumor can be regarded as a cell mass with a biologic hierarchy that is orchestrated by cancer stem cells. The specific features of cancer stem cells may result from a series of gene expression regulatory mechanisms. As important regulatory factors of gene expression, microRNAs (miRNAs) have critical roles in the self-renewal, pluripotency, differentiation, and tumorigenicity of cancer stem cells. However, the effects of animal miRNAs on cancer stem cells have not been investigated extensively. Here, we report that miRNA of a shrimp, Marsupenaeus japonicus (mja-miR-35-3p), which possesses antiviral activity in shrimp, could suppress the proliferation of melanoma and breast cancer stem cells, but not cancer nonstem cells, by arresting the cell cycle in the G₁ phase and inducing apoptosis. Shrimp mja-miR-35-3p (named mja-miR-35) targets the human peptidylprolyl cis/trans isomerase, never in mitosis gene a-interacting 1 (PIN1) gene, which is up-regulated in cancer stem cells. The results indicated that PIN1 silencing caused cell cycle arrest in the G₁ phase, induced apoptosis, and decreased the sphere-forming capacity of cancer stem cells, but not cancer nonstem cells, showing that PIN1 had beneficial effects against the stemness of cancer stem cells. The in vivo data revealed that shrimp mja-miR-35 suppressed the stemness of cancer stem cells in mice by inhibiting the PIN1 antiapoptotic-cell cycle pathway. These findings demonstrated that the miRNAs of aquatic animals might be an important source for discovering human antitumor drugs.-Zhang, S., Zhang, X. Shrimp miRNA suppresses the stemness of human cancer stem cells via the PIN1 pathway.

Keywords: cross-species; human PIN1; shrimp mja-miR-35; tumorigenesis.