The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNASeq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats. We catalogue the expression proﬁles of 40,064 genes, 65,167 transcripts, 31,909 alternatively spliced transcript variants and 2,367 non-coding genes/non-coding RNAs (ncRNAs) annotated in AceView. We ﬁnd that organ-enriched, differentially expressed genes reﬂect the known organ-speciﬁc biological activities. A large number of transcripts show organ-speciﬁc, age-dependent or sex-speciﬁc differential expression patterns. We create a web-based, open-access rat BodyMap database of expression proﬁles with crosslinks to other widely used databases, anticipating that it will serve as a primary resource for biomedical research using the rat model.
Abstract Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression
Breast cancer is the most frequentlydiagnosed cancer in women in western countries, and it is the second most common cause of cancer-related deaths . Despite recent improvements in the diagnosis and management of early disease, approximately 50% of women with breast cancer will develop distant metastases .
Lung cancer is the leading cause of cancer-related mortality worldwide. The majority of lung cancers are sporadic, and familial cases are extremely rare. Previous studies have mainly focused on sporadic lung cancer and identified a large quantity of driver genes. However, familial lung cancers are rarer and studied less. The present study recruited a Chinese family in which multiple members had developed lung squamous carcinoma. To find the causative mutations, whole exome sequencing was conducted using a peripheral blood sample of one lung squamous carcinoma patient, and certain variants were validated in more samples. Whole exome sequencing analysis obtained ~2.0 Gb of data (an average of 60x depth for each targeted base), and further validation experiments identified two functional variants in two cancer‑related genes (c.1218delA:p.E406fs in PDE4DIP and C1342A:p.L448I in CLTCL1). This study therefore provides useful sources for the further study of hereditary lung cancer.
The mechanisms underlying hypermethylation of tumor-suppressor gene promoters in cancer is not well understood. Here, we report that lysine acetylation of the oncogenic transcription factor STAT3 is elevated in tumors. We also show that genetically altering STAT3 at Lys685 reduces tumor growth, which is accompanied by demethylation and reactivation of several tumor-suppressor genes. Moreover, mutating STAT3 at Lys685 disrupts DNA methyltransferase 1–STAT3 interactions in cultured tumor cells and in tumors. These observations are conﬁrmed by treatment with an acetylation inhibitor, resveratrol. Furthermore, reduction of acetylated STAT3 in triple-negative breast cancer cells leads to demethylation and activation of the estrogen receptor-α gene, sensitizing the tumor cells to antiestrogens. Our results also demonstrate a correlation between STAT3 acetylation and methylation of estrogen receptor-α in melanoma, which predicts melanoma progression. Taken together, these results suggest a role of STAT3 acetylation in regulating CpG island methylation, which may partially explain aberrant gene silencing in cancer. These ﬁndings also provide a rationale for targeting acetylated STAT3 for chemoprevention and cancer therapy.
How B cells affect cancer is uncertain. Yu and colleagues demonstrate that CD5 binds to IL-6 and induces STAT3 activation in the absence of IL-6Ra in B cells. In mouse tumor models, CD5+ but not CD5– B cells promote tumor growth, and this association was also observed in several types of human tumors.
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