microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection

Abstract

In BriefZhao et al. identify microRNA-222 as a mediator of mitochondrial dysfunction, THBS1, and CD47 induced during TGEV infection and showed that mi-croRNA-222 inhibits TGEV-induced mitochondrial dysfunction via targeting and downregulating CD47. Graphical Abstract Highlights• microRNA-222 attenuates TGEV-induced mitochondrial dysfunction.• microRNA-222 downregulates THBS1 and CD47.• THBS1 is the target of microRNA-222 during TGEV infection.• THBS1 and CD47 increase mitochondrial Ca 2ϩ level and reduced mitochondrial membrane potential (MMP). Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. Our previous research showed that TGEV infection could induce mitochondrial dysfunction and upregulate miR-222 level. Therefore, we presumed that miR-222 might be implicated in regulating mitochondrial dysfunction induced by TGEV infection. To verify the hypothesis, the effect of miR-222 on mitochondrial dysfunction was tested and we showed that miR-222 attenuated TGEV-induced mitochondrial dysfunction. To investigate the underlying molecular mechanism of miR-222 in TGEV-induced mitochondrial dysfunction, a quantitative proteomic analysis of PK-15 cells that were transfected with miR-222 mimics and infected with TGEV was per-formed. In total, 4151 proteins were quantified and 100 differentially expressed proteins were obtained (57 upregulated, 43 downregulated), among which thrombospondin-1 (THBS1) and cluster of differentiation 47 (CD47) were downregulated. THBS1 was identified as the target of miR-222. Knockdown of THBS1 and CD47 decreased mitochondrial Ca 2؉ level and increased mitochondrial membrane potential (MMP) level. Reversely, overexpression of THBS1 and CD47 elevated mitochondrial Ca 2؉ level and reduced mitochondrial membrane potential (MMP) level. Together, our data establish a significant role of miR-222 in regulating mitochondrial dysfunction in response to TGEV infection.

MiR‐222 inhibits apoptosis in porcine follicular granulosa cells by targeting the THBS1 gene

“…The results of the bioinformatic analysis and luciferase assay demonstrate that miR‐222 directly binds to the 3′UTR of THBS1 . In a recent study, quantitative proteomic analysis of miR‐222‐mimic‐transfected and TGEV‐infected PK‐15 cells revealed that THBS1 is a target for miR‐222 (Zhao et al, ). This result is consistent with those of the present study.…”

“…Several previous studies have identified a number of miRNAs that regulate the THBS1 gene in different types of cells, e.g., miR‐487b, the miR‐17‐92 cluster, miR‐194, miR‐18 and miR‐19, miR‐27b, and miR‐let‐7d (Asama et al, ; Dogar, Semplicio, Guennewig, & Hall, ; Farberov & Meidan, ; Feng et al, ; Miao et al, ; Sundaram et al, ; van Almen et al, ). In a recent study, a quantitative proteomic analysis of PK‐15 cells that were transfected with miR‐222 mimics and infected with transmissible gastroenteritis virus (TGEV) indicated that THBS1 was regulated by miR‐222 (Zhao et al, ). However, there are few reports of miR‐222 in pGCs.…”

MOTS-c repairs myocardial damage by inhibiting the CCN1/ERK1/2/EGR1 pathway in diabetic rats

“…Overexpression of ATF3 results in accumulation of depolarized mitochondria, and increased mitochondrial ROS production ( 37 ). In addition, Zhao et.al ( 38 ) reported that overexpression of THBS1 stimulated mitochondrial Ca 2+ levels and decreased mitochondrial membrane potential (MMP) levels, leading to mitochondrial dysfunction. These data strongly suggests that MOTS-c improves mitochondrial function.…”

Integrated miRNA and mRNA Expression Profiles Reveal Differentially Expressed miR-222a as an Antiviral Factor Against Duck Hepatitis A Virus Type 1 Infection

“…A previous study implicates elevated let-7f-5p expression as a biomarker for multiple malignant diseases, including non-muscle-invasive bladder ( Shee et al., 2020 ) and prostate cancers ( Ge et al., 2020 ). miR-222a, a miR-221/222 cluster component ( Chun-Zhi et al., 2010 ), is aberrantly expressed in hepatocellular carcinoma ( Wang et al., 2019 ), epithelial tumors ( Gaetani et al., 2020 ), and virus-infected cells ( Zhao et al., 2019 ; Song et al., 2020 ). Therefore, we speculate that they may be prospective candidates for antibacterial treatments or use as prophylactic targets.…”