Lnc2Cancer 2.0 (http://www.bio-bigdata.net/lnc2cancer) is an updated database that provides comprehensive experimentally supported associations between lncRNAs and human cancers. In Lnc2Cancer 2.0, we have updated the database with more data and several new features, including (i) exceeding a 4-fold increase over the previous version, recruiting 4989 lncRNA-cancer associations between 1614 lncRNAs and 165 cancer subtypes. (ii) newly adding about 800 experimentally supported circulating, drug-resistant and prognostic-related lncRNAs in various cancers. (iii) appending the regulatory mechanism of lncRNA in cancer, including microRNA (miRNA), transcription factor (TF), variant and methylation regulation. (iv) increasing more than 70 high-throughput experiments (microarray and next-generation sequencing) of lncRNAs in cancers. (v) Scoring the associations between lncRNA and cancer to evaluate the correlations. (vi) updating the annotation information of lncRNAs (version 28) and containing more detailed descriptions for lncRNAs and cancers. Moreover, a newly designed, user-friendly interface was also developed to provide a convenient platform for users. In particular, the functions of browsing data by cancer primary organ, biomarker type and regulatory mechanism, advanced search following several features and filtering the data by LncRNA-Cancer score were enhanced. Lnc2Cancer 2.0 will be a useful resource platform for further understanding the associations between lncRNA and human cancer.

Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined. The core set of genes relating to histone methylation (KMT2D, KMT2C, EZH2), histone acetylation (CREBBP, EP300), DNA methylation (TET2), and chromatin remodeling (ARID1A) were detected in the training cohort of 316 patients by whole-genome/exome sequencing (WGS/WES) and in the validation cohort of 303 patients with newly diagnosed DLBCL by targeted sequencing. Their correlation with peripheral blood immune cells and clinical outcomes were assessed. Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo. Among all 619 DLBCL patients, somatic mutations in KMT2D (19.5%) were most frequently observed, followed by mutations in ARID1A (8.7%), CREBBP (8.4%), KMT2C (8.2%), TET2 (7.8%), EP300 (6.8%), and EZH2 (2.9%). Among them, CREBBP/EP300 mutations were significantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios, as well as inferior progression-free and overall survival. In B-lymphoma cells, the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation, downregulated FBXW7 expression, activated the NOTCH pathway, and downstream CCL2/CSF1 expression, resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation. In B-lymphoma murine models, xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation, higher M2 macrophage recruitment, and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.

MicroRNAs (miRNAs) are endogenous, small, noncoding single-stranded RNA molecules approximately 22 nucleotides in length. miRNAs are involved in the post-transcriptional regulation of various important cellular physiological and pathological processes, including cell proliferation, differentiation, apoptosis, and hormone biosynthesis and secretion. Ovarian follicles are the key functional units of female reproduction, and the development of these follicles is a complex and precise process accompanied by oocyte maturation as well as surrounding granulosa cell proliferation and differentiation. Numerous miRNAs expressed in the ovary regulate ovarian follicle growth, atresia, ovulation and steroidogenesis and play an important role in ovarian disorders. This review considers recent advances in the identification of miRNAs involved in the regulation of ovarian function as well as the possible influence of miRNAs on ovarian-derived disorders, such as ovarian cancer, polycystic ovarian syndrome and premature ovarian failure. An improved understanding of the regulation of ovarian function by miRNAs may shed light on new strategies for ovarian biology and ovarian disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0162-2) contains supplementary material, which is available to authorized users.