Shrimp miRNA suppresses the stemness of human cancer stem cellsviathe 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, Marsupenαeus jαponicus (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. FASEB J. 33, 10767–10779 (2019). http://www.fasebj.org

Molecular Chaperones in Cancer Stem Cells: Determinants of Stemness and Potential Targets for Antitumor Therapy

“…It was discussed that such a liposomal nanoplatform-based approach may be exploited in vivo for silencing cyclophilin A expression in glioma cells to overcome their stemness [202]. Another very original approach has been reported by Zhang and Zhang [203], who used microRNA (mja-miR-35) isolated from a shrimp, Marsupenaeus japonicus, to silence the PIN1 gene in human CSCs. As a result of the action of mja-miR-35, PIN silencing was selectively achieved in melanoma CSCs and breast CSCs, which was accompanied by impairment of their spheroid-forming ability and stimulation of their apoptotic death [203].…”

“…Another very original approach has been reported by Zhang and Zhang [203], who used microRNA (mja-miR-35) isolated from a shrimp, Marsupenaeus japonicus, to silence the PIN1 gene in human CSCs. As a result of the action of mja-miR-35, PIN silencing was selectively achieved in melanoma CSCs and breast CSCs, which was accompanied by impairment of their spheroid-forming ability and stimulation of their apoptotic death [203]. This implies that microRNAs from aquatic animals may successfully be used to oppose stemness in human malignancies.…”

Characterization of Host lncRNAs in Response to Vibrio splendidus Infection and Function as Efficient miRNA Sponges in Sea Cucumber

“…As well known, miRNAs are considered to regulate gene expression by binding to the 3’UTRs (untranslated regions) of target mRNAs ( 16 ). In a previous study, 8 miRNAs (miR-9, miR-31, miR-124, miR-133, miR-137, miR-200, miR-210 and miR-2008) were found to participate in the sea cucumber immune response under Vibrio splendidus infection ( 17 ).…”

“…Vibrio splendidus is one of devastating sea cucumber pathogens, its virulence is particularly high in infected sea cucumber, leading to severe mortalities reach 90% within 7 days of infection ( 14 ). As well known, host ncRNAs are considered to be key regulators of pathogen-host interactions ( 15 , 16 ). Deep sequencing revealed that eight miRNAs were differentially expressed between healthy and SUS-diseased sea cucumbers, in which miR-31, a highly conserved miRNA that regulate cell apoptosis by targeting AjCTRP9 in Vibrio splendidus -challenged Apostichopus japonicus ( 17 , 18 ).…”

Double‐edged sword role of shrimp miRNA explains an evolutionary language between shrimp‐pathogen interactions that unties the knot of shrimp infection

“…Use of shrimp microRNA as a source of tumour‐targeting agents could be a novel approach in drug discovery. A shrimp miRNA called mja‐miR‐35‐3p (also named mja‐miR‐35) has been found to suppress the proliferation of cancer stem cells by inhibiting peptidylprolyl cis/trans isomerase, never in mitosis gene a–interacting 1 (PIN1) 148 . Shrimp miR‐S8 degrades YB‐1 transcript, and shrimp miR‐965 disrupts the myeloid cell leukaemia sequence‐1‐endoplasmic reticulum stress‐X‐box‐binding protein 1 (MCL‐1‐ER stress‐XBP1) feedback loop, both suppress the tumour progression of human melanoma stem cells 149,150 .…”