Biology subjects

Jing Tang

Publications and source records attributed to Jing Tang.

3 recordsLinked to original sources

bioRxiv2016

Natural Variation in Arabidopsis Cvi-0 Accession Uncovers Regulation of Guard Cell CO2 Signaling by MPK12

Plant gas exchange is regulated by guard cells that form stomatal pores. Stomatal adjustments are crucial for plant survival; they regulate uptake of CO2 for photosynthesis, loss of water and entrance of air pollutants such as ozone. We mapped ozone hypersensitivity, more open stomata and stomatal CO2-insensitivity phenotypes of the Arabidopsis thaliana accession Cvi-0 to a single amino acid substitution in MAP kinase 12 (MPK12). In parallel we showed that stomatal CO2-insensitivity phenotypes of a mutant cis (CO2-insensitive) were caused by a deletion of MPK12. Lack of MPK12 impaired bicarbonate-induced activation of S-type anion channels. We demonstrated that MPK12 interacted with the protein kinase HT1, a central node in guard cell CO2 signaling, and that MPK12 can function as an inhibitor of HT1. These data provide a new function for plant MPKs as protein kinase inhibitors and suggest a mechanism through which guard cell CO2 signaling controls plant water management.

Plant Biology↗

bioRxiv2016

Methods for High-Throughput Drug Combination Screening and Synergy Scoring

Gene products or pathways that are aberrantly activated in cancer but not in normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials but so far showed limited efficacy mostly due to variability in treatment responses and often rapidly emerging resistance. Towards more effective treatment options, we will critically need multi-targeted drugs or drug combinations, which selectively inhibit the cancer cells and block distinct escape mechanisms for the cells to become resistant. Functional profiling of drug combinations requires careful experimental design and robust data analysis approaches. At the Institute for Molecular Medicine Finland (FIMM), we have developed an experimental-computational pipeline for high-throughput screening of drug combination effects in cancer cells. The integration of automated screening techniques with advanced synergy scoring tools allows for efficient and reliable detection of synergistic drug interactions within a specific window of concentrations, hence accelerating the identification of potential drug combinations for further confirmatory studies.

Systems Biology↗

bioRxiv2016

Recurrently deregulated lncRNAs associated with HCC tumorigenesis and metastasis revealed by genomic, epigenomic and transcriptomic profiling in paired primary tumor and PVTT samples

Hepatocellular carcinoma (HCC) are highly potent to invade the portal venous system and subsequently develop into the portal vein tumor thrombosis (PVTT). PVTT could induce intrahepatic metastasis, which is closely associated with poor prognosis. A comprehensive systematic characterization of long noncoding RNAs (lncRNAs) associated with HCC metastasis has not been reported. Here, we first assayed 60 clinical samples (matched primary tumor, adjacent normal tissue, and PVTT) from 20 HCC patients using total RNA sequencing. We identified and characterized 8,603 novel lncRNAs from 9.6 billion sequenced reads, indicating specific expression of these lncRNAs in our samples. On the other hand, the expression patterns of 3,212 known and novel recurrently deregulated lncRNAs (in >=20% of our patients) were well correlated with clinical data in a TCGA cohort and published liver cancer data. Some lncRNAs (e.g., RP11-166D19.1/MIR100HG) were shown to be useful as putative biomarkers for prognosis and metastasis. Moreover, matched array data from 60 samples showed that copy number variations (CNVs) and alterations in DNA methylation contributed to the observed recurrent deregulation of 716 lncRNAs. Subsequently, using a coding-noncoding co-expression network, we found that many recurrently deregulated lncRNAs were enriched in clusters of genes related to cell adhesion, immune response, and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. The results of our integrative analysis provide a valuable resource regarding functional lncRNAs and novel biomarkers associated with HCC tumorigenesis and metastasis.

Genomics↗