Estrogen plays a critical role in breast cancer (BC) progression through estrogen receptor (ER)-mediated gene regulation. Emerging studies suggest that the malignant progress of BC cells is influenced by the cross talk between microRNAs (miRNAs) and ER-α signaling. However, the mechanism and functional linkage between estrogen and miRNAs remain unclear. The expression levels of miR-196a and SPRED1 in BC were tested by qRT-PCR in 46 paired BC and adjacent tissues and by the GEO datasets. The role of miR-196a in estrogen-induced BC development was examined by CCK-8 assay, wound healing assay, Matrigel invasion assay and tumorigenicity assay in nude mice. The binding site of ER-α in miR-196a promoter region was analyzed by ChIP-seq, ChIP assay and luciferase reporter assay. The potential targets of miR-196a in BC cells were explored using the luciferase reporter assay and western blot analysis, and the correlation between miR-196a and SPRED1 was analyzed by Spearman’s correlation analysis in BC specimens and GEO dataset. TCGA BRCA data was used to characterize the ESR1 signatures according to MSigDB gene set. The expression levels of miR-196a were higher in ER-positive (ER+) breast tumors compared to ER-negative (ER-) tumor tissue samples. Besides, miR-196a was involved in estrogen-induced BC cell proliferation, migration and invasion. Notably, the up-regulation of miR-196a was mediated by a direct interaction with estrogen receptor α (ER-α) but not estrogen receptor β (ER-β) in its promoter region, and miR-196a expression levels were positively correlated to ER-α signature scores. Furthermore, SPRED1 was a new direct target of miR-196a which participated in miR-196a-promoted BC development and was suppressed by ligand-activated ER-α signal pathway. Finally, forced expression of miR-196a induced tumor growth of MCF7 cells, while inhibition of miR-196a significantly suppressed the tumor progress in vivo. Overall, the identification of estrogen/miR-196a/SPRED1 cascade will shed light on new molecular mechanism of estrogen signaling in BC development and therapy.

Objectives: Glioblastoma multiforme (GBM) is considered the most assailant subtype of gliomas, presenting a formidable obstacle because of its inherent resistance to temozolomide (TMZ). This study aimed to characterize the function of lncRNA NEAT1 in facilitating the advancement of gliomas.Methods: The expression level of NEAT1 in glioma tissues and cells was detected by qRT‐PCR. RNA interference experiment, cell proliferation assay, FITC/PI detection assay, immunoblotting, bioinformatics prediction, a double luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, SLDT assay and correlation analysis of clinical samples were performed to explore the regulatory effects of NEAT1, miR‐454‐3p and Cx43 and their role in malignant progression of GBM. The role of NEAT1 in vivo was investigated by an intracranial tumor formation experiment in mice.Results: The results showed that recurring gliomas displayed elevated levels of NEAT1 compared to primary gliomas. The suppression of NEAT1 led to a restoration of sensitivity in GBM cells to TMZ. NEAT1 functioned as a competitive endogenous RNA against miR‐454‐3p. Connexin 43 was identified as a miR‐454‐3p target. NEAT1 was found to regulate gap junctional intercellular communication by modulating Connexin 43, thereby impacting the response of GBM cells to TMZ chemotherapy. Downregulation of NEAT1 resulted in enhanced chemosensitivity to TMZ and extended the survival of mice.Conclusions: Overall, these results indicated that the NEAT1/miR‐454‐3p/Connexin 43 pathway influences GBM cell response to TMZ and could offer a potential new strategy for treating GBM.

Australia and New Zealand have the highest worldwide CRC incidence with CRC being the 2^nd most commonly diagnosed cancer and the 3^rd most common cause of cancer death among both men and women. CRC is a complex disease arising from the impact of environmental factors, including diet and lifestyle choices on different genetic backgrounds. Obesity and type 2 diabetes are significant risk factors for CRC, the levels of which are increasing in Australia. As a consequence CRC is projected to increase, being the most common Australian cancer by 2025. While the association of obesity with CRC has been reported by a number of studies, the mechanism\s that contribute to CRC development in the context of obesity are unknown. Understanding these mechanisms and potential genetic susceptibility is crucial for developing effective intervention and screening strategies. Recent evidence suggests that gut microbial communities are altered in obese individuals, resulting in a change in the predominant species and overall loss of community diversity but it is unknown if these changes impact CRC development or progression. We have established a comprehensive tissue, blood and microbial collection from 150 lean and obese colorectal cancer patients in the Hunter Region, Australia and commenced an integrative pilot next generation sequencing project to begin to unravel the link between obesity and CRC. Twelve individuals (6 lean and 6 obese) were selected for complementary next-generation sequencing; generating matched sequencing data sets (Total RNA-seq, Poly A RNA-seq, microbial RNA-seq and exome-seq) from normal colon, colon tumor, adipose and digesta samples samples. For this purpose, we have developed a method for simultaneously isolating human and microbial RNA from gut lumen of sufficient quality and quantity from limited material. Results presented will evaluate the differences in host and microbial transciptomics in normal colon and tumor tissue of lean and obese individuals with CRC and methodological comparisons between Total RNA-seq and Poly A RNA-seq will be reported. Citation Format: Desma M. Grice, Denis C. Bauer, Konsta Duesing, Dongmei Li, Paul Greenfield, Sarah Nielsen, Brian Draganic, Steve Smith, Peter Pockney, Rodney Scott, Garry N. Hannan. Human and microbial transcriptomics from lean and obese individuals with colorectal cancer: A comparison of Total and Poly A RNA sequencing from clinical samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-237. doi:10.1158/1538-7445.AM2013-LB-237

Water extract of Semiliquidambar cathayensis (WESC) exhibits favorable therapeutic effects against depression, yet its pharmacodynamic material basis and mechanism of action remain unclear. In this study, ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) was employed to analyze the chemical constituents of WESC. Network pharmacology and molecular docking were further applied to screen the antidepressant mechanism basis and potential targets of WESC. Lipopolysaccharide (LPS)‐induced mouse and PC12 cell models were established as in vivo depressive animal model and in vitro cellular injury model, respectively. Combined with pathological examination and molecular biological techniques, the antidepressant mechanism of WESC was systematically investigated. Results showed that a total of 14 chemical components were identified from WESC. Network pharmacology and molecular docking analyses indicated that GSK3β was one of the key targets, and the active components in WESC possessed strong binding affinities with GSK3β, Axin1, and NF‐κB. Pathological studies demonstrated that WESC significantly alleviated inflammatory infiltration in the mouse prefrontal cortex and hippocampal neuronal damage. Molecular biological analyses revealed that WESC markedly downregulated the expression of proteins related to the GSK3β/NF‐κB signaling pathway in LPS‐stimulated mice and PC12 cells, thereby attenuating neuroinflammation, promoting neural plasticity, and exerting antidepressant effects.