Shrimp Antiviral mja-miR-35 Targets CHI3L1 in Human M2 Macrophages and Suppresses Breast Cancer Metastasis

Abstract

Virus infection can change host's metabolism, while tumorigenesis results from metabolic disorder. MicroRNAs (miRNAs), crucial regulatory factors overlaying transcriptional control mechanisms, can guide metabolic homeostasis. In terms of metabolic disorder, antiviral miRNAs may have anti-tumor activity. However, this issue has not been extensively investigated. In the present study, the results revealed that shrimp mja-miR-35, which showed antiviral activity in shrimp against white spot syndrome virus (WSSV) infection, could suppress the metastasis of breast cancer by targeting human CHI3L1 gene of M2 macrophages in a cross-phylum manner. Furthermore, the feed expressing shrimp mja-miR-35 had antiviral capacity in shrimp and anti-tumor activity in humans, leading to the simultaneous control of virus infection and tumor progression. Therefore, our findings indicated that the antiviral miRNAs derived from shrimp stress responses against virus infection might be an important source of human anti-tumor drugs and miRNAs could bridge the control of aquaculture diseases and the prevention of human tumors.

Shrimp miRNA suppresses the stemness of human cancer stem cellsviathe PIN1 pathway

“…In a previous study, a total of 15 miRNAs, including mja-miR- 35, with no homologs in other animals were identified; thus, these miRNAs might be specific to shrimp (20). Shrimp mja-miR-35, which is up-regulated in shrimp in response to white spot syndrome virus challenge, showed antiviral activity against white spot syndrome virus infection in shrimp (21). As previously reported in refs.…”

Non-coding RNA-related antitumor mechanisms of marine-derived agents

“…Similar to mja-miR-35, shrimp miR-34 and mja-miR-35 are two other WSSV-associated miRNAs whose expression can be upregulated by the virus, which then suppress the virus by targeting the viral genes wsv330 and wsv359 or wsv140, wsv279, wsv309, and wsv361, respectively ( Cui et al, 2017 ; Chen et al, 2018b ; Cui et al, 2021 ). Overexpression of shrimp miR-34 or mja-miR-35 in human breast cancer cells significantly suppressed cell metastasis in vitro and in vivo ( Cui et al, 2017 ; Chen et al, 2018b ).…”

“…Similar to mja-miR-35, shrimp miR-34 and mja-miR-35 are two other WSSV-associated miRNAs whose expression can be upregulated by the virus, which then suppress the virus by targeting the viral genes wsv330 and wsv359 or wsv140, wsv279, wsv309, and wsv361, respectively ( Cui et al, 2017 ; Chen et al, 2018b ; Cui et al, 2021 ). Overexpression of shrimp miR-34 or mja-miR-35 in human breast cancer cells significantly suppressed cell metastasis in vitro and in vivo ( Cui et al, 2017 ; Chen et al, 2018b ). The molecular mechanism of shrimp miR-34 against human tumors was shown to be related to shrimp miR-34-mediated expression of multiple human tumor-related genes, including cyclin D1 (CCND1), cyclin dependent kinase 6 (CDK6), cyclin E2 (CCNE2), E2F transcription factor 3 (E2F3) FOS-like antigen-1 (FOSL1), and hepatocyte growth factor receptor (MET) ( Cui et al, 2017 ), while the tumor suppressor function of mja-miR-35 is achieved by targeting M2 macrophages and human chitinase-3-like protein 1 (CHI3L1) ( Chen et al, 2018b ).…”

Metabolic reprogramming in crustaceans: A vital immune and environmental response strategy

“…Similarly, in IHHNV-infected P. vannamei, significantly dysregulated metabolites such as glucose, lactic acid, triacylglycerides and cholesterol were found in the plasma and hepatopancreas, suggesting that the virus modulates host metabolic pathways to maximize the use of these metabolites for replication. 59 Although several viral pathogens infect and cause diseases in crustaceans, viral-induced metabolic reprogramming have thus far been associated with WSSV, [60][61][62][63][64][65][66][67] TSV 58 and IHHNV. 59 During viralhost interactions, the survival of crustacean hosts depends on the ability to counteract viral-induced metabolic changes and to mount a robust immune response against the invading pathogen 68 or exploit these metabolic changes to its advantage.…”

“…Although several viral pathogens infect and cause diseases in crustaceans, viral‐induced metabolic reprogramming have thus far been associated with WSSV, 60–67 TSV 58 and IHHNV 59 . During viral–host interactions, the survival of crustacean hosts depends on the ability to counteract viral‐induced metabolic changes and to mount a robust immune response against the invading pathogen 68 or exploit these metabolic changes to its advantage.…”