The advent of effective targeted therapeutics has led to increasing emphasis on precise biomarkers for accurate patient stratification. Here, we describe the role of ACK1, a non-receptor tyrosine kinase in abrogating migration and invasion in KRAS mutant lung adenocarcinoma. Bosutinib, which inhibits ACK1 at 2.7 nM IC50, was found to inhibit cell migration and invasion but not viability in a panel of non-small cell lung cancer (NSCLC) cell lines. Knockdown of ACK1 abrogated bosutinib-induced inhibition of cell migration and invasion specifically in KRAS mutant cells. This finding was further confirmed in an in vivo zebrafish metastatic model. Tissue microarray data on 210 Singaporean lung adenocarcinomas indicate that cytoplasmic ACK1 was significantly over-expressed relative to paired adjacent non-tumor tissue. Interestingly, ACK1 expression in “normal” tissue adjacent to tumour, but not tumour, was independently associated with poor overall and relapse-free survival. In conclusion, inhibition of ACK1 with bosutinib attenuates migration and invasion in the context of KRAS mutant NSCLC and may fulfil a therapeutic niche through combinatorial treatment approaches.

Indigenous cattle in Sichuan Province, southwestern China, provide abundant genetic resources. However, their genetic diversity and population structure remain largely unknown, especially on the genome-wide scale. In the present study, we successfully employed the restriction site-associated DNA sequencing approach (RADseq) to explore genome-wide SNPs among six breeds of Sichuan cattle. A total of 238,725 high-confidence SNPs were finally obtained with a mean distance of 11,140 bp between two adjacent sites, and 43.4% were revealed to be novel in comparison with a public reference database of genetic variants. The mean nucleotide diversity and polymorphism information content (PIC) among all six breeds were 0.1878 and 0.1555, respectively. Pingwu and Ganzi cattle showed the highest and lowest genetic diversity, respectively. The inter-breed comparisons revealed that Ganzi and Ebian cattle were obviously separate from the others. Our reference set of genome-wide SNPs specific to indigenous cattle in Sichuan is the first of its kind. Moreover, our set can be used to investigate the genetic diversity and population structure and for genome-wide association studies.

Background: To examine the prevalence of the Paraoxonase1 (PON1) gene 192Q/R polymorphism amongst Singaporean Chinese with Alzheimer's disease (AD) and mixed dementia and possible clinical associations. Methods: We examined the presence of the PON1 192Q/R polymorphism together with cognitive status, functional status and neuropsychiatric symptoms among 186 older Singaporean Chinese with AD (n = 109) and mixed dementia (n = 77). Results: The R allele predominated in 67% of the AD patients and 63.1% of the patients with mixed dementia. Within the mixed dementia subgroup, the R allele was significantly associated with a higher BADLS score, NPI-Q scores and CDR scores. Conclusion: Among older Singaporean Chinese with AD and mixed dementia, the R allele was predominant. In particular, within the mixed dementia subgroup, the R allele carrier status was associated with poorer functional status, greater presence of neuropsychiatric symptoms and a more severe stage of dementia. Further studies should be conducted.

Background In eukaryotic organisms, it has been well acknowledged that 3′ untranslated regions (3′ UTRs) of mRNA are actively involved in post-transcriptional regulations of gene expression. Although both shortening and lengthening of 3′ UTRs of specific candidate genes were explicitly documented to have functional consequences, landscape of 3′ UTR lengths in relation to evolutionary dynamics and biological meanings remains to be elucidated when large-scale data become available. Objectives The primary objective of this study was to revealed different inter- and intra-species patterns on length distribution of 3′ UTRs in comparison with 5′ UTRs and coding regions. Methods In the present study, we investigated 3′ UTR lengths in a highly curated set of 57,135 mRNA sequences among four well-studied and taxonomically diverse metazoan species (fruit fly, zebrafish, mouse and human). Results The average length ratio of 3′–5′ UTRs considerably increased from fruit fly (twofold) to human (fivefold). Moreover, genes can be characterized by the obviously different patterns of evolutionary change on 3′ UTR lengths. By utilizing the Gene Ontology annotations, genes with differential lengths of 3′ UTRs were suggested to have the divergent functional implications. In human, we further revealed that ubiquitously transcribed genes had higher median lengths of 3′ UTRs than the genes of tissue-restricted expressions. Conclusion We conducted a comprehensive analysis and provided an overview regarding 3′ UTRs biology of mRNAs in animals, whereas the mechanistic explanations of 3′ UTRs length variation in correlation to regulation of gene expression still remain to be further studied. Electronic supplementary material The online version of this article (10.1007/s13258-019-00808-8) contains supplementary material, which is available to authorized users.