A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats

The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance.However,the genetic basis of muscle development in the Boer goat remains obscure.In this study,we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development.A total of9 959 autosomal copy number variations(CNVs) were identified through selection signal analysis in 127 goat genomes.Specifically,we confirmed that the highest signal CNV(HSV) was a chromosomal arrangement containing an approximately 1.11 Mb(CHIR17:60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region(CHIR17:60145940-60151302 bp) with overlapping genes(e.g.,ARHGAP10,NR3C2,EDNRA,PRMT9,and TMEM184C).The homozygous duplicated HSV genotype(+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats.The expression network of three candidate genes(ARHGAP10,NR3C2,and EDNRA)regulating dose transcription was constructed by RNA sequencing.Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells(SMSCs) and their overexpression significantly increased the expression of SAA3.The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.

Amyloid precursor protein regulates 5-fluorouracil resistance in human hepatocellular carcinoma cells by inhibiting the mitochondrial apoptotic pathway

Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality globally.It accounts for the majority of primary liver cancer cases.Amyloid precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and metastasis.Therefore,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were performed.The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 cells.Through successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control group.Furthermore,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells.Mechanistically,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.