Novel long non‐coding RNA CYB561‐5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non‐small cell lung cancer

Abnormally expressed long non‐coding RNAs (lncRNAs) have been recognized as potential diagnostic biomarkers or therapeutic targets in non‐small cell lung cancer (NSCLC). The role of the novel lnc‐CYB561‐5 in NSCLC and its specific biological activity remain unknown. In this study, lncRNAs highly expressed in NSCLC tissue samples compared with paired adjacent normal tissue samples and atypical adenomatous hyperplasia were identified by RNA‐seq analysis. Lnc‐CYB561‐5 is highly expressed in human NSCLC and is associated with a poor prognosis in lung adenocarcinoma. In vivo, downregulation of lnc‐CYB561‐5 significantly decreases tumour growth and metastasis. In vitro, lnc‐CYB561‐5 knockdown treatment inhibits cell migration, invasion and proliferation ability, as well as glycolysis rates. In addition, RNA pulldown and RNA immunoprecipitation (RIP) assays show that basigin (Bsg) protein interacts with lnc‐CYB561‐5. Overall, this study demonstrates that lnc‐CYB561‐5 is an oncogene in NSCLC, which is involved in the regulation of cell proliferation and metastasis. Lnc‐CYB561‐5 interacts with Bsg to promote the expression of Hk2 and Pfk1 and further lead to metabolic reprogramming of NSCLC cells.     

基于转录组的肝豆状核变性调控网络的构建和分析

本研究旨在利用生物信息学方法构建经铜诱导的ATP7B基因敲除HepG2细胞系的转录调控网络。探讨关键转录因子在肝豆状核变性发生、发展中的潜在作用机制。收集公共基因表达数据库(gene expression omnibus, GEO)中包含野生型、ATP7B基因敲除型、铜诱导的野生型和铜诱导的ATP7B基因敲除型HepG2细胞系数据。筛选由铜诱导产生的差异表达基因(differentially expressed genes,DEGs)后进行基因本体论(gene ontology,GO)、京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)富集分析。基于蛋白相互作用网络,识别疾病关键基因和功能模块,并对关键功能模块中的基因进行富集分析。最后,构建转录调控网络,筛选核心转录因子。共筛选出1 034个差异表达基因,其中上调525个,下调509个。上、下调关键功能模块分别包括了3785个和3931个基因。关键功能模块中的基因主要定位于细胞-基质连接、染色体、剪接复合体、核糖体等区域,共同参与了mRNA加工、组蛋白修饰、RNA剪切...     

新疆准噶尔盆地玛湖凹陷玛页1井宾夕法尼亚亚系至乌拉尔统风城组孢粉地层学研究

提要准噶尔盆地西北缘玛湖凹陷风城组主要形成于碱湖环境,含有优质生烃母岩。对玛页1井风城组岩心样品的孢粉分析建立了Protohaploxypinus perfectus–Lunatisporites tersus (PT)孢粉组合。该组合包括20属29种孢粉化石。PT组合以双气囊具肋花粉占主导,蕨类孢子含量很低为特征;孢粉母体植物类群以裸子植物门种子蕨盾籽目为主,其次为松柏纲松柏目。该组合与准噶尔盆地南缘塔什库拉组上部至乌拉泊组的Crustaesporites–Protohaploxypinus–Hamiapollenites孢粉组合可以对比,均以双气囊具肋花粉为主要特征,又同时出现重要的属种Gardenasporites bilabiatus,Triangulisaccites boleensis和Hamiapollenites saccatus。孢粉地层学和同位素年代学资料表明,玛页1井风城组PT组合的时代很可能属于石炭纪宾夕法尼亚亚纪卡西莫夫期至二叠纪乌拉尔世阿瑟尔期,玛湖凹陷区整个风城组沉积时代晚于宾夕法尼亚亚纪巴什基尔期,其上部可能包含部分乌拉尔世阿瑟尔期沉积。风城组黑色页岩中...     

TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer

Tumor necrosis factor α stimulated gene 6 (TSG-6), a 30-KD secretory protein, plays an essential role in modulating inflammatory responses and extracellular matrix remodeling. However, little is known regarding the role of TSG-6 in human cancers. Here, we investigated the mechanism of action and the role of TSG-6 in colorectal cancer (CRC) metastasis. We found that TSG-6 was highly expressed in tumor tissues and was associated with poor prognosis and metastasis in CRC. Mechanistically, TSG-6 overexpression in CRC cells resulted in ERK activation and epithelial-mesenchymal transition by means of stabilizing CD44 and facilitating the CD44-EGFR complex formation on the cell membrane. Consequently, this resulted in the promotion of tumor migration and invasion both in vitro and in vivo. Notably, our data showed that CRC cells secreted TSG-6 could trigger a paracrine activation of JAK2-STAT3 signaling and reprogram normal fibroblasts into cancer-associated fibroblasts, which exhibited upregulation of pro-metastatic cytokines (CCL5 and MMP3) and higher movement ability. In animal models, the co-injection of cancer cells and TSG6-reprogrammed fibroblasts led to a significant increase in tumor metastasis. Our findings indicated that TSG-6 overexpression in CRC cells could promote cancer metastasis in both an autocrine and paracrine manner. Therefore, targeting TSG-6 might be a potential therapeutic strategy for the treatment of metastatic CRC.     

Piwi/piRNAs control food intake by promoting neuropeptide F expression in locusts

Animal feeding, which directly affects growth and metabolism, is an important physiological process. However, the contribution of PIWI proteins and PIWI‐interacting RNAs (piRNAs) to the regulatory mechanism of animal feeding is unknown. Here, we report a novel function of Piwi and piRNAs in regulating food intake in locusts. Our study shows that the locust can serve as a representative species for determining PIWI function in insects. Knockdown of Piwi1 expression suppresses anabolic processes and reduces food consumption and body weight. The reduction in food intake by knockdown of Piwi1 expression results from decreased expression of neuropeptide NPF1 in a piRNA‐dependent manner. Mechanistically, intronic piRNAs might enhance RNA splicing of NPF1 by preventing hairpin formation at the branch point sites. These results suggest a novel nuclear PIWI/piRNA‐mediated mechanism that controls food intake in the locust nervous system.     

Camptothecin effectively treats obesity in mice through GDF15 induction

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight through activation of hindbrain receptor glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) in rodents and nonhuman primates, thus endogenous induction of this peptide holds promise for obesity treatment. Here, through in silico drug-screening methods, we found that small molecule Camptothecin (CPT), a previously identified drug with potential antitumor activity, is a GDF15 inducer. Oral CPT administration increases circulating GDF15 levels in diet-induced obese (DIO) mice and genetic ob/ob mice, with elevated Gdf15 expression predominantly in the liver through activation of integrated stress response. In line with GDF15’s anorectic effect, CPT suppresses food intake, thereby reducing body weight, blood glucose, and hepatic fat content in obese mice. Conversely, CPT loses these beneficial effects when Gdf15 is inhibited by a neutralizing antibody or AAV8-mediated liver-specific knockdown. Similarly, CPT failed to reduce food intake and body weight in GDF15’s specific receptor GFRAL-deficient mice despite high levels of GDF15. Together, these results indicate that CPT is a promising anti-obesity agent through activation of GDF15-GFRAL pathway.

Elevated circulating levels of growth differentiation factor 15 (GDF15) have been shown to reduce food intake and lower body weight in rodents and nonhuman primates. This study reveals that the small molecule Camptothecin induces endogenous GDF15, suppressing food intake and reducing body weight in obese mice, suggesting a promising candidate for anti-obesity treatment.     

屯昌猪MYLPF基因序列分析及其组织表达量检测

为获得屯昌猪MYLPF基因的CDS区序列并分析其分子结构特征,研究屯昌猪、杜洛克猪以及其杂交F1代猪不同组织中的MYLPF mRNA表达水平,本研究以GenBank上公布的猪MYLPF基因序列(登录号:NM_001006592)为参考设计引物,通过RT-PCR扩增、测序获得屯昌猪MYLPF基因CDS区.结果显示:该基因...