Ferroptosis in Cancer Progression: Role of Noncoding RNAs

Ferroptosis is a novel form of programmed cell death, and it is characterized by iron-dependent oxidative damage, lipid peroxidation and reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence and that abundant ferroptosis in cells can inhibit tumor progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long noncoding RNAs, and circular RNAs, have been shown to be involved in biological processes of ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism of this phenomenon is still unclear. To clarify this issue, increasing studies have focused on the regulatory roles of ncRNAs in the initiation and development of ferroptosis and the role of ferroptosis in progression of various cancers, such as lung, liver, and breast cancers. In this review, we systematically summarized the relationship between ferroptosis-associated ncRNAs and cancer progression. Moreover, additional evidence is needed to identify the role of ferroptosis-related ncRNAs in cancer progression. This review will help us to understand the roles of ncRNAs in ferroptosis and cancer progression and may provide new ideas for exploring novel diagnostic and therapeutic biomarkers for cancer in the future.     

马铃薯遗传转化体系的优化及玉米淀粉分支酶基因SBEⅡb的导入

以马铃薯脱毒试管苗茎段为转化受体材料,建立并优化了农杆菌介导的马铃薯遗传转化体系。通过农杆菌介导法将玉米淀粉分支酶基因(Starch branching enzyme b,SBEⅡb)的过表达载体转化马铃薯,接种762个茎段,共获得35株抗性植株。经PCR检测获得了4株转基因阳性植株;对转基因植株进一步进行GUS活性组织化学染色,发现转基因植株的茎段与试管薯均被染上蓝色,表明外源SBEⅡb基因已整合到马铃薯基因组,且正常表达。     

中国贵州宽阔水自然保护区蚋相初报及三新种描述(双翅目,蚋科)(英文)

首次记载贵州省宽阔水自然保护区蚋科Simuliidae14种,并记述其中3新种,包括遵义蚋Simulium(Simulium)zunyiense sp.nov.和新尖板蚋Simulium(Simulium)neoacontum sp.nov.以及隶属于山蚋亚属Simulium(Montisimulium)的离板山蚋Simulium(Montisimulium)separatum sp.nov.。模式标本存放于贵阳医学院生物学教研室。遵义蚋,新种S.(S.)zunyiense sp.nov.(图1～13)隶属于蚋亚属杂色蚋组variegatum group,与本组已知近缘种主要区别在雄尾结构,如生殖肢端节,生殖腹板和中骨的形状特殊。正模♂,贵州遵义市宽阔水自然保护区(28°12’N,107°18’E;海拔1483m),2010-09-20,修江帆,陈黔采。词源:新种种名源自模式产地。新尖板蚋,新种S.(S.)neoacontum sp.nov.(图14～19)隶属于蚋亚属淡足蚋组malyschevi group,与尖板蚋S.(S.)acontum Clen et al.,近似,但雄虫生殖肢端节,生殖腹板和中骨的形状迥异,此外,其呼吸丝排列方式也有明显差异。正模♂,贵州宽阔水自然保护区让水(28°17’N,107°08’E;海拔682m),2010-08-13,修江帆采。词源:新种种名源自其形态极似尖板蚋S.(S.)acontum,冠以"neo"以示区别。离板山蚋,新种S.(Montisimulium)separatum sp.nov.(图20～28)隶属于山蚋亚属Subgenus Montimulium与绒丝山蚋S.(M.)nemoriragum(Datta,1973)近似,主要区别是雌虫生殖板内缘远离,蛹呼吸丝背对具短茎。此外,幼虫头扇毛和肛鳃次生叶数目也有明显差异。正模♀,贵州宽阔水自然保护区大洞(28°12’N,107°18’E;海拔1483m),2010-08-20,修江帆,陈黔采。词源:新种种名源自其雌虫生殖板内缘分离。     

Long Non-coding RNA ANRIL Downregulation Alleviates Neuroinflammation in an Ischemia Stroke Model via Modulation of the miR-671-5p/NF-κB Pathway

Neurochemical Research - The aim of this study was to investigate the role and underlying mechanism of the long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus, ANRIL) in ischemia...     

Upregulation of LRRC8A by m5C modification-mediated mRNA stability suppresses apoptosis and facilitates tumorigenesis in cervical cancer

Cervical cancer (CC) is one of the most common gynecological malignancies with poor prognosis for advanced CC patients. LRRC8A is a volume-regulated anion channel protein involved in cellular homeostasis, but its role in CC remains largely unknown. In this study, we found that LRRC8A is elevated in CC and associated with poor prognosis. LRRC8A maintains cell survivals under the hypotonic condition, and promotes tumorigenesis through apoptosis suppression in vitro and in vivo. Notably, LRRC8A is upregulated by NSUN2-mediated m⁵C modification. m⁵C modified-LRRC8A mRNA is bound by the RNA binding protein YBX1 followed by the increased RNA stability. Moreover, loss of NSUN2 suppresses the proliferation and metastasis of CC cells, and NSUN2 expression is positively correlated with LRRC8A expression in CC. Altogether, our study demonstrates that the NSUN2-m⁵C-LRRC8A axis is crucial and would be a potential therapeutic target for CC.     

The circadian regulation of extracellular ATP

Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.     

Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins

Nature’s fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5’s active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases.     

The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics

Cytoplasmic dynein is a multisubunit, minus end-directed microtubule motor that uses dynactin as an accessory complex to perform various in vivo functions including vesicle transport, spindle assembly, and nuclear distribution [1]. We previously showed that in the filamentous fungus Aspergillus nidulans, a GFP-tagged cytoplasmic dynein heavy chain (NUDA) forms comet-like structures that exhibited microtubule-dependent movement toward and back from the hyphal tip [2]. Here we demonstrate that another protein in the NUDA pathway, NUDF, which is homologous to the human LIS1 protein involved in brain development [3, 4], also exhibits such dynamic behavior. Both NUDA and NUDF are located at the ends of microtubules, and this observation suggests that the observed dynamic behavior is due to their association with the dynamic microtubule ends. To address whether NUDA and NUDF play a role in regulating microtubule dynamics in vivo, we constructed a GFP-labeled alpha-tubulin strain and used it to compare microtubule dynamics in vivo in wild-type A. nidulans versus temperature-sensitive loss-of-function mutants of nudA and nudF. The mutants showed a lower frequency of microtubule catastrophe, a lower rate of shrinkage during catastrophe, and a lower frequency of rescue. The microtubules in the mutant cells also paused longer at the hyphal tip than wild-type microtubules. These results indicate that cytoplasmic dynein and the LIS1 homolog NUDF affect microtubule dynamics in vivo.