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Functional analysis of prv-miR-LLT11a encoded by pseudorabies virus
Huimin Liu,Li Yang,Zhibin Shi,Ruiqi Lv,Xia Yang,Chuanqing Wang,Lu Chen,Hongtao Chang 대한수의학회 2019 Journal of Veterinary Science Vol.20 No.6
Viral-encoded microRNAs (miRNAs) play have vital roles in the regulations of virus replications and host immune responses. The results of previous studies have indicated that miRNA clusters are involved in the replication and virulence of the pseudorabies virus (PRV), which may potentially lead to the immune escape or facilitation of PRV replications. This study's previous research revealed that the prv-mirmiR-LLT11a was differentially expressed during PRV infections. The present study's results have demonstrated that the prv-miR-LLT11a could significantly inhibit PRV replications. It was further determined that SLA-1 was the target gene of the prv-miR-LLT11a, and simultaneously, thate overexpression of prv-miR-LLT11a could down-regulate the mRNA and protein levels of SLA-1 in a dose-independent manner. Furthermore, the present study also found observed that the prv-miR-LLT11a canhad also down-regulated the TAP1 expressions. Our findings provide a better understanding of the molecular mechanism involved in on the effects of prv-miR-LLT11a on SLA-1 and TAP1, as well as and its involvement in a potential immune system evasion of PRV.
Gan Junqing,Liu Shan,Zhang Yu,He Liangzi,Bai Lu,Liao Ran,Zhao Juan,Guo Madi,Jiang Wei,Li Jiade,Li Qi,Mu Guannan,Wu Yangjiazi,Wang Xinling,Zhang Xingli,Zhou Dan,Lv Huimin,Wang Zhengfeng,Zhang Yanqiao,Q 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.