Enhanced biomass and thermotolerance of Arabidopsis by SiERECTA isolated from Setaria italica L

Foxtail millet is commonly used as a food and forage grass. ERECTA (ER) is a receptor-like kinase that can improve plant biomass and stress resistance. The sorghum SbER10_X1 gene was used as a probe to identify ER family genes on the Setaria italica genomes (SiERs), and determine the characteristics of the SiERs family. Herein, the structural features, expression patterns, and thermotolerance of SiERs function were identified by bioinformatics analysis, real-time PCR and transgenesis estimation. Results showed that SiERs had four members: two members were located on chromosome 1 with a total of six copies (SiER1_X1, SiER1_X2, SiER1_X3, SiER1_X4, SiER1_X5, and SiER1_X6), and two were on chromosome 4, namely, SiER4 (SiER4_X1 and SiER4_X2) and SiERL1. Among them, SiER1_X4 and SiER4_X1 were expressed highest in above-ground organs of foxtail millet, and actively responded to treatments with abscisic acid, brassinolide, gibberellin, and indole acetic acid. After overexpression of SiER1_X4 and SiER4_X1 in Arabidopsis, the plant height and biomass of the transgenic Arabidopsis significantly increased. Following high-temperature treatment, transgenic seedlings survived better compared to wild type. Transgenic lines showed higher SOD and POD activities, and expression level of AtHSF1 and AtBl1 genes significantly increased. These results indicated that SiER1_X4 and SiER4_X1 played important regulatory roles in plant growth and thermotolerance. The two genes provide potential targets for conventional breeding or biotechnological intervention to improve the biomass of forage grass and thermotolerance of field crops

The prognostic significance of CXCL1 hypersecretion by human colorectal cancer epithelia and myofibroblasts.

BackgroundClinical therapy for metastatic colorectal cancer (CRC) remains limited, especially when the tumor harbors a KRAS mutation. This study aimed to identify prognostic biomarkers in CRC that are accessible for therapeutic inhibition.MethodsConditioned media from human CRC epithelial cells and myofibroblasts were screened by cytokine arrays for tumorigenic factors. The protein and mRNA expressions of these factors were determined by immunohistochemistry and gene microarrays in human CRC tissues. Prognostic biomarkers were determined by correlation of mRNA expression to overall survival in stage IV CRC patients. Inhibition of CXCL1 was performed with specific neutralizing antibody and lentiviral shRNAs. Malignant growth was assessed by soft agar growth assays and xenograft tumor growth in immunocompromised mice.ResultsCXCL1 was highly secreted by KRAS mutant human CRC cells and myofibroblasts in a complementary adaptive response to serum deprivation. Elevated CXCL1 level promoted anchorage-independent growth of murine fibroblasts and human CRC cells. Inhibition of CXCL1 by neutralizing antibody and specific shRNAs decreased CRC tumor growth. Highly elevated CXCL1 expression significantly correlated with decreased overall survival in stage IV CRC patients (hazard ratio 0.28; 95% CI 0.11-0.72).ConclusionsHigh CXCL1 expression is a poor prognostic biomarker in metastatic CRC. CXCL1 inhibition suppressed tumorigenic growth of KRAS mutant CRC cells

MOESM1 of The prognostic significance of CXCL1 hypersecretion by human colorectal cancer epithelia and myofibroblasts

Additional file 1: Figure S1. Microarray gene expressions of NIH3T3 cells and human CRC. (A) CXCL1, CXCR2 and DARC mRNA levels in NIH3T3 cells. (B) CXCL1 mRNA levels showed low inverse correlation with TNM stages of primary human CRC. (C) IL8 mRNA levels did not show correlation with TNM stages of primary human CRC. S.I. represented arbitrary unit of signal intensity

Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature

Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome. The fourth tumor was an adrenocortical carcinoma, which has rarely been reported previously in Lynch syndrome. Three of our 4 patients carried a pathogenic germ-line mutation in a mismatch repair gene. The unusual tumor in each of the 3 patients showed loss of the mismatch repair protein corresponding to the mutation. The fourth patient did not have mutation information but had a history of colonic and endometrial carcinomas; both lacked MSH2 and MSH6 proteins. Interestingly, none of the 4 unusual tumors revealed microsatellite instability on polymerase chain reaction testing, whereas an appendiceal carcinoma from 1 of the study patients who was tested simultaneously did. The recognition of such tumors expands the repertoire of usable test samples for the workup of high-risk families. As yet, however, there are no data to support the inclusion of these tumors into general screening guidelines for detecting Lynch syndrome, nor are there data to warrant surveillance for these tumors in patients with Lynch syndrome

Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res

Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments

Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation.

Aberrant Wnt signaling can drive cancer development. In many cancer types, the genetic basis of Wnt pathway activation remains incompletely understood. Here, we report recurrent somatic mutations of the Drosophila melanogaster tumor suppressor-related gene FAT1 in glioblastoma (20.5%), colorectal cancer (7.7%), and head and neck cancer (6.7%). FAT1 encodes a cadherin-like protein, which we found is able to potently suppress cancer cell growth in vitro and in vivo by binding β-catenin and antagonizing its nuclear localization. Inactivation of FAT1 via mutation therefore promotes Wnt signaling and tumorigenesis and affects patient survival. Taken together, these data strongly point to FAT1 as a tumor suppressor gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer. Loss of FAT1 function is a frequent event during oncogenesis. These findings address two outstanding issues in cancer biology: the basis of Wnt activation in non-colorectal tumors and the identity of a 4q35 tumor suppressor