Evaluating the impact of test-trace-isolate for COVID-19 management and alternative strategies.

There are many contrasting results concerning the effectiveness of Test-Trace-Isolate (TTI) strategies in mitigating SARS-CoV-2 spread. To shed light on this debate, we developed a novel static-temporal multiplex network characterizing both the regular (static) and random (temporal) contact patterns of individuals and a SARS-CoV-2 transmission model calibrated with historical COVID-19 epidemiological data. We estimated that the TTI strategy alone could not control the disease spread: assuming R0 = 2.5, the infection attack rate would be reduced by 24.5%. Increased test capacity and improved contact trace efficiency only slightly improved the effectiveness of the TTI. We thus investigated the effectiveness of the TTI strategy when coupled with reactive social distancing policies. Limiting contacts on the temporal contact layer would be insufficient to control an epidemic and contacts on both layers would need to be limited simultaneously. For example, the infection attack rate would be reduced by 68.1% when the reactive distancing policy disconnects 30% and 50% of contacts on static and temporal layers, respectively. Our findings highlight that, to reduce the overall transmission, it is important to limit contacts regardless of their types in addition to identifying infected individuals through contact tracing, given the substantial proportion of asymptomatic and pre-symptomatic SARS-CoV-2 transmission.

Pin1 impairs microRNA biogenesis by mediating conformation change of XPO5 in hepatocellular carcinoma.

MicroRNA (miRNA) dysregulation is associated with the tumorigenesis and development of numerous human cancers. The defect in miRNA biogenesis is the main cause of miRNA dysregulation. We previously demonstrated that ERK-induced phosphorylation of XPO5 followed by peptidyl-prolyl cis/trans isomerase Pin1-mediated isomerization downregulates miRNA expression and contributes to hepatocellular carcinoma (HCC) development. However, how Pin1 precisely regulates miRNA biogenesis in HCC remains elusive. Here we reveal that Pin1 has a pivotal role in the miRNA maturation process by modulating phosphorylated Serine-Proline (pS-P) motif of XPO5 in a phosphorylation-dependent manner. By recognizing and binding to XPO5 via its WW domain, Pin1 catalyzes the conformation change of XPO5 and diminishes XPO5 ability to export pre-miRNAs from the nucleus to the cytoplasm, resulting in the reduced mature miRNA levels and promoted HCC development. Furthermore, downregulation of Pin1 by shRNA restores XPO5-dependent pre-miRNA export and effective biogenesis of mature miRNAs, leading to both in vitro and in vivo HCC inhibition. Therefore, our research discloses a new posttranscriptional regulatory mechanism of miRNA biosynthesis and provides the experimental basis for a novel HCC therapy by targeting Pin1.

Long non-coding RNA linc00460 promotes epithelial-mesenchymal transition and cell migration in lung cancer cells.

Long non-coding RNAs (lncRNAs) function as critical regulators to participate in tumor progression and metastasis. However, their roles in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that the expression of the lncRNA linc00460 is significantly upregulated in NSCLC tumors and associated with poor prognosis for NSCLC patients, implying that linc00460 is important for lung cancer development. The accurate transcription initiation and termination sites of linc00460 were then identified by rapid-amplification of cDNA ends (RACE) technologies, and the sequencing data demonstrated that linc00460, predominantly located in the cytoplasm of lung cancer cells, is a novel transcript variant. Functional studies through gain- and loss-of-function strategies showed that linc00460 promotes cell migration and invasion through inducing epithelial-mesenchymal transition in lung cancer cells, whereas it has no effect on cell proliferation. The mechanism investigations through RNA pull-down assay and mass spectrometry identified that hnRNP K physically interacts with linc00460, and it also participates in cell migration and invasion. Therefore, our findings suggest that linc00460 acts as an oncogene in NSCLC to promote cell migration and highlight the potential prognostic and therapeutic values of linc00460 for NSCLC patients.