Oral squamous cell carcinoma (OSCC), as the most common type of oral cancer, is responsible for almost 3% of all malignant tumors worldwide. Non‐coding RNAs such as lncRNAs and microRNAs have been ...involved in many cancers including OSCC. Recently, lncRNA metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) has been reported to play an oncogenic role in OSCC metastasis. However, the underlying mechanism of MALAT1 in regulating OSCC progression remains unclear. The aim of this study was to investigate the specific role of MALAT1 in OSCC development. It was observed that MALAT1 was upregulated in OSCC cell lines. Inhibition of MALAT1 can prevent OSCC proliferation while overexpressing MALAT1 promoted OSCC progression. In addition, bioinformatics search was used to identify that miR‐125b was a direct target of MALAT1, which indicated a negative correlation between MALAT1 and miR‐125b. Besides these, STAT3 was predicted as a binding target of miR‐125b in OSCC. Overexpression of MALAT1 was able to suppress the tumor inhibitory effect of miR‐125b mimics via upregulating STAT3. Moreover, the function of MALAT1 in OSCC development was further investigated by using in vivo assays. The established nude mice models revealed that downregulated MALAT1 greatly inhibited OSCC tumor growth and reversely upregualated MALAT1 promoted OSCC development via miR‐125b/STAT3 axis, respectively. In conclusion, MALAT1 can function as a competing endogenous RNA (ceRNA) to modulate STAT3 expression by absorbing miR‐125b in OSCC and could be used as a novel therapeutic target in OSCC diagnosis and treatment.
Our findings in OSCC cell lines and xenografts suggested MALAT1 as an oncogene, which can promote OSCC development. This was the first report to demonstrate that MALAT1 can function as a ceRNA and modulate STAT3 expression by sponging miR‐125b in OSCC both in vitro and in vivo. Our data indicated that MALAT1 could be used as a therapeutic target in OSCC diagnosis and treatment.
Dendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical ...polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm
with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse ...cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real‐time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa‐miR‐933 overexpression. hsa_circRNA_100533 binds to hsa‐miR‐933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533‐miR‐933‐GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.
We revealed that hsa_circRNA_100533 might exert its antitumor function by competitively binding with miR‐933, and then regulated the expression GNAS. Thus, hsa_circRNA_100533 might be an effective diagnostic biomarker and therapeutic target for patients with oral squamous cell carcinoma.
Long noncoding RNA (lncRNA) exerts a potential regulatory role in tumorigenesis. LncRNA TUG1 expression remains high in oral squamous cell carcinoma (OSCC) tissues. However, its biological mechanism ...in OSCC remains unknown. In this study, TUG1 expression in OSCC cells was detected by quantitative real‐time polymerase chain reaction. Proliferative and migratory potentials of OSCC cells were determined by Cell Counting Kit 8, 5‐Ethynyl‐2′‐ deoxyuridine (EdU), and Transwell assay, respectively. We identified the potential target of TUG1 through bioinformatics and dual‐luciferase reporter gene assay. Furthermore, their interaction and functions in regulating the development of OSCC were clarified by western blot and RNA immunoprecipitation assay. Our results demonstrated a high expression of TUG1 in OSCC cells. Overexpression of TUG1 markedly accelerated proliferative and migratory potentials of OSCC cells. Besides, TUG1 could positively regulate the expression of distal‐less homeobox 1 (DLX1) by competing with miR‐524‐5p. These results indicated that TUG1 participated in the development of OSCC as a competing endogenous RNA to competitively bind to miR‐524‐5p and thus mediate DLX1 expression.
Our study verified that upregulated TUG1 increased expression of distal‐less homeobox 1 (DLX1), the target gene of miR‐524‐5p, further leading to abnormal proliferation and migration of oral squamous cell carcinoma (OSCC) cells. TUG1 functioned as a competitive endogenous RNA to regulate DLX1 expression by sponging miR‐524‐5p, thus regulating the development of OSCC.
The continuous increase of the greenhouse gas nitrous oxide (N2O) in the atmosphere due to increasing anthropogenic nitrogen input in agriculture has become a global concern. In recent years, ...identification of the microbial assemblages responsible for soil N2O production has substantially advanced with the development of molecular technologies and the discoveries of novel functional guilds and new types of metabolism. However, few practical tools are available to effectively reduce in situ soil N2O flux. Combating the negative impacts of increasing N2O fluxes poses considerable challenges and will be ineffective without successfully incorporating microbially regulated N2O processes into ecosystem modeling and mitigation strategies. Here, we synthesize the latest knowledge of (i) the key microbial pathways regulating N2O production and consumption processes in terrestrial ecosystems and the critical environmental factors influencing their occurrence, and (ii) the relative contributions of major biological pathways to soil N2O emissions by analyzing available natural isotopic signatures of N2O and by using stable isotope enrichment and inhibition techniques. We argue that it is urgently necessary to incorporate microbial traits into biogeochemical ecosystem modeling in order to increase the estimation reliability of N2O emissions. We further propose a molecular methodology oriented framework from gene to ecosystem scales for more robust prediction and mitigation of future N2O emissions.
This review summarizes the major microbial pathways of soil N2O production, and key environmental factors modulating their relative contributions, and further proposes to use a combination of state-of-the-art approaches for better source partitioning and incorporation of microbial datasets to achieve better predictive ecosystem models.
Statins: a repurposed drug to fight cancer Jiang, Wen; Hu, Jin-Wei; He, Xu-Ran ...
Journal of experimental & clinical cancer research,
07/2021, Letnik:
40, Številka:
1
Journal Article
Recenzirano
Odprti dostop
As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their ...lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.
Aim
Mitochondrial autophagy (mitophagy) clears damaged mitochondria and attenuates ischemic neuronal injury. Urolithin A (Uro‐A) activates mitophagy in mammal cells and Caenorhabditis elegans. We ...explored neuroprotection of Uro‐A against ischemic neuronal injury.
Methods
Mice were subjected to middle cerebral artery occlusion. The brain infarct and neurological deficit scores were measured. The N2a cells and primary cultured mice cortical neurons were subjected to oxygen‐glucose deprivation and reperfusion (OGD/R). Uro‐A was incubated during OGD/R, and cell injury was determined by MTT and LDH. Autophagosomes were visualized by transfecting mCherry‐microtubule‐associated protein 1 light chain 3 (LC3). The protein levels of LC3‐II, p62, Translocase Of Inner Mitochondrial Membrane 23 (TIMM23), and cytochrome c oxidase subunit 4 isoform 1 (COX4I1) were detected by Western blot. The ER stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were determined by reverse transcription‐polymerase chain reaction (RT‐PCR).
Results
Urolithin A alleviated OGD/R‐induced injury in N2a cells and neurons and reduced ischemic brain injury in mice. Uro‐A reinforced ischemia‐induced autophagy. Furthermore, Uro‐A‐conferred protection was abolished by 3‐methyladenine, suggesting the requirement of autophagy for neuroprotection. However, mitophagy was not further activated by Uro‐A. Instead, Uro‐A attenuated OGD/R‐induced ER stress, which was abolished by 3‐methyladenosine. Additionally, neuroprotection was reversed by ER stress inducer.
Conclusion
Urolithin A protected against ischemic neuronal injury by reinforcing autophagy rather than mitophagy. Autophagy activation by Uro‐A attenuated ischemic neuronal death by suppressing ER stress.
Cerebral ischemia-reperfusion (I-R) is a complex pathological process. Although autophagy can be evoked by ischemia, its involvement in the reperfusion phase after ischemia and its contribution to ...the fate of neurons remains largely unknown. In the present investigation, we found that autophagy was activated in the reperfusion phase, as revealed in both mice with middle cerebral artery occlusion and oxygen-glucose deprived cortical neurons in culture. Interestingly, in contrast to that in permanent ischemia, inhibition of autophagy (by 3-methyladenine, bafilomycin A
1
, Atg7 knockdown or in atg5
−/−
MEF cells) in the reperfusion phase reinforced, rather than reduced, the brain and cell injury induced by I-R. Inhibition of autophagy either with 3-methyladenine or Atg7 knockdown enhanced the I-R-induced release of cytochrome c and the downstream activation of apoptosis. Moreover, MitoTracker Red-labeled neuronal mitochondria increasingly overlapped with GFP-LC3-labeled autophagosomes during reperfusion, suggesting the presence of mitophagy. The mitochondrial clearance in I-R was reversed by 3-methyladenine and Atg7 silencing, further suggesting that mitophagy underlies the neuroprotection by autophagy. In support, administration of the mitophagy inhibitor mdivi-1 in the reperfusion phase aggravated the ischemia-induced neuronal injury both in vivo and in vitro. PARK2 translocated to mitochondria during reperfusion and Park2 knockdown aggravated ischemia-induced neuronal cell death. In conclusion, the results indicated that autophagy plays different roles in cerebral ischemia and subsequent reperfusion. The protective role of autophagy during reperfusion may be attributable to mitophagy-related mitochondrial clearance and inhibition of downstream apoptosis. PARK2 may be involved in the mitophagy process.
PDF
