Biological roles of LSD1 beyond its demethylase activity.

It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention.

hsa_circ_0072309 Expression Profiling in Non-small-Cell Lung Carcinoma and Its Implications for Diagnosis and Prognosis.

Circular RNAs (circRNAs), which fall into the category of endogenous ncRNAs, are linked to disease progression of neoplastic diseases. Whereas, it remains uncharacterized regarding hsa_circ_0072309's function and implications in lung carcinoma (LC). Gene Expression Omnibus (GEO) database was utilized for identifying circRNAs with aberrantly expression in LC. qRT-PCR was responsible for determining hsa_circ_0072309 levels in lung adenocarcinoma (LAC). Also, its involvement in LC cell progression was investigated. Experimentally, hsa_circ_0072309 was identified as one of the most aberrantly down-regulated circRNAs in the GEO database (GSE101684 and GSE112214). qRT-PCR revealed notably down-regulated hsa_circ_0072309 in LAC tissue, which had a close association with adverse 3-year survival, as well as LNM and advanced TNM stage. Based on ROC, the AUC of hsa_circ_0072309 was determined to be 0.887, and its specificity and susceptibility can be improved by combined detection of either CYFRA21-1 or CEA. In a word, hsa_circ_0072309 is lowly expressed in lung cancer patients and the survival rate of lowly expressed patients is significantly lower, a candidate marker with prognostic utility for the disease.

The Effects of Lentinan on the Expression Patterns of ß-Catenin, Bcl-2, and Bax in Murine Bone Marrow Cells Are Associated with Enhancing Dectin-1.

This study was focused on investigating the effect of lentinan (LNT) on the expression patterns of ß-catenin, Bcl-2, and Bax in murine bone marrow cells (BMCs). Adult BALB/L mice were divided into four groups (n = 10 for each group) that consisted of normal control adult BALB/L mice (control group) and adult BALB/L mice with intraperitoneal injection of low, medium, and high doses of LNT (LLen, MLen, and HLen, respectively). Cells of bone marrow from adult BALB/L mice were cultured in DMEM medium with or without laminarin (inhibitor of dectin-1) to investigate the role of dectin-1 in the effect of lentinan on the expression profile of ß-catenin, Bcl-2, and Bax using western blotting and RT-PCR methods. The ELISA results indicated that the expression profiles of dectin-1 were significantly elevated in BMCs from groups of LLen, MLen, and HLen compared with the control group (P < 0.05). The protein and gene expression profiles of ß-catenin and Bax increased significantly in murine BMCs from groups of MLen and HLen compared with the control group or the LLen group (P < 0.05). In contrast, the protein and gene expression levels of Bcl-2 decreased significantly in BMCs from the LLen, MLen, and HLen groups compared with the control group (P < 0.05). Furthermore, the expression profiles of ß-catenin, Bcl-2, and Bax reversed with the administration of laminarin (P < 0.05). Taken together, our results identified that the changing expression profiles of ß-catenin, Bcl-2, and Bax in murine BMCs are associated with enhancing dectin-1.