N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A ...modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study ...revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.
Wet deposition fluxes of mercury (Hg) species were estimated during the period from June 2010 to July 2011 at 3 sites in core urban areas in Chongqing, China. Rain water was collected by automatic ...deposition sampler for total Hg (THg) and methylmercury (MeHg) analyses. Our results showed that annual wet deposition fluxes of THg and MeHg were 28.7 ± 5.1 and 0.28 ± 0.09 μg m−2 yr−1, respectively. We estimate that MeHg wet deposition contributes 9.2–19.6% of the total MeHg flux to a local reservoir. Cumulative THg fluxes collected from nine principal rainfall events (>1.5 μg m−2 yr−1) at three sampling sites accounted for 20% of annual overall THg wet deposition. Statistical analyses yielded significant relationship between rainfall amounts and Hg wet deposition fluxes (r2 = 0.76, p < 0.01 for THg; r2 = 0.65, p < 0.01 for MeHg), suggesting that rainfall is one of the most important factors controlling the Hg fluxes. Obvious seasonal variations of THg fluxes were observed, with the maximum value occurring in summer (accounting for 40% of total annual THg deposition) while minimum values occurred in winter in all the three sampling sites. 72-h backward trajectory analysis on nine large deposition events at the three sites, using HYSPLIT model indicated that most of air masses which contain a relatively high precipitation amount and pass through major Hg sources would have an elevated Hg load.
•MeHg loading from the atmosphere to local water body cannot be ignored.•Rainfall is an important factor on driving the THg and MeHg deposition fluxes.•THg and MeHg wet deposition fluxes showed a seasonal variation.
Paenibacillus polymyxa
is an important member of the plant growth-promoting rhizobacteria.
P. polymyxa
YC0136 inoculation had beneficial effect on growth promotion and biological control of tobacco (
...Nicotiana tabacum
L.) under field conditions. This study aimed to reveal the growth-promoting mechanisms of strain YC0136. In growth-promotion assays, tobacco plant height was increased by 8.42% and 8.25% at 60 and 90 days, respectively, after inoculation with strain YC0136. Strain YC0136 also promoted the accumulation of tobacco biomass in varying degrees. Following inoculation with strain YC0136, 3,525 and 4,368 tobacco genes were up-regulated and down-regulated, respectively. Strain YC0136 induced the expression of plant hormone-related genes in tobacco, including auxin, cytokinin, and gibberellin, as well as transcription factors related to stress resistance such as WRKY and MYB. In addition, strain YC0136 induced the up-regulation of genes in the phenylpropanoid biosynthesis pathway by 1.51–4.59 times. Interaction with tobacco also induced gene expression changes in strain YC0136, with 286 and 223 genes up-regulated and down-regulated, respectively. Tobacco interaction induced up-regulation of the
ilvB
gene related to auxin biosynthesis in strain YC0136 by 1.72 times and induced expression of some nutrient transport genes. This study contributes to our understanding of the growth-promoting mechanisms of strain YC0136 on tobacco and provides a theoretical basis for the application of
P. polymyxa
YC0136 as a biological fertilizer.
Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription ...regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of β-catenin. Taken together, our data identified a miR-4524b-5p/WTX/β-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-purity solanesol can be used for pharmaceutical applications, but the current method for purifying solanesol has high cost and difficult continuous operation, and the use of molecular imprinting ...to purify natural products is a hot research topic of current research. Solanesol molecularly imprinted polymers were synthesized via emulsion polymerization for the first time. The morphology of the SSO-MIPs was observed with a scanning electron microscope, and the effects of the synthesis time, initiator dosage, functional monomer dosage, and cross-linking agent dosage on the adsorption effects under high-temperature and rapid synthesis conditions were discussed. The results demonstrate that the optimum synthesis conditions were a ratio of the template molecules to the functional monomers to the cross-linking agents of 1:8:30 (mol:mol:mol), 10 mg of the initiator, and a synthesis temperature of 70 °C. The imprinting factor of SSO-MIPs synthesized under the optimized process was found to reach 2.51, and the SSO-MIPs synthesized by this method exhibited a good adsorption effect, emitted less pollution during the synthesis process, and are convenient for demulsification. This research reports a reliable method for the synthesis of solanesol molecularly imprinted polymers.
Two novel 3-decalinoyltetramic acid (3DTA) derivatives, namely fusarisetins C and D (
and
), and four known derivatives (
) were isolated from the marine-derived fungus
D39. Their structures were ...determined by spectroscopic data, vibrational circular dichroism (VCD) calculations, and X-ray crystallography. Compound
was identified as the first fusarisetin to possess an unprecedented carbon skeleton with a tetracyclic ring system comprised of a decalin moiety (6/6) and a tetramic acid moiety. A plausible biosynthetic pathway for the isolated compounds was proposed. All 3DTAs derivatives exhibited a potent phytotoxicity, and
also displayed a remarkable anti-phytopathogenic activity superior to the positive control resulting in damage of the cell membrane of
and ensuing leakage of the intracellular components. Here, the phytotoxicity of fusarisetins has been reported for the first time. The OSMAC fermentation optimization approach to give
was performed by varying the culture media and salinities. The results showed that potato liquid medium with 1% salinity is the most favorable condition for the production of
.
Abstract
Natural rhizosphere bacteria has the potential to act as an alternative of chemical pesticides for sustainable agriculture. In the current study, tobacco rhizosphere
Bacillus velezensis
D ...exhibited great antibacterial effect against
Ralstonia solanacearum
, and significantly enhanced the tobacco resistance against bacterial wilt in pot experiments. Then
Bacillus velezensis
D was labeled with
gfp
marker and found to stably colonize in tobacco root, the colonization density of strain D in root still remained 5.33 × 10
4
CFU/gat 30 days post-inoculation. Subsequently, field trials for two years (2021–2022) showed the control effects of the strain D on the tobacco bacterial wilt were 12.26% and 36.37%, respectively, indicating the application of
B. velezensis
D could improve plant resistance to
R.solanacearum
. In order to further study the antibacterial activities of strain D, effects of the crude extracts on the swimming ability, cell viability and the morphology of
R. solanacearum
were analyzed. The results showed that the crude extracts reduced the motility of
R. solanacearum
, and caused cell wall rupture and cell death. Furthermore, MALDI-TOF-MS and HPLC-QTOF-MS analysis indicated that lipopeptides (fengycin and iturin) and polyketides (bacillaene) were detected in the crude extracts of strain D. Based on these findings, we speculated that
Bacillus velezensis
D firstly colonized in tobacco root, then produced antibacterial substances at ecological sites to exert antagonistic effects, inhibiting motility traits of
R. solanacearum
and damaging the cell well. Hence,
Bacillus velezensis
D could be used as a potential biological control agents against tobacco bacterial wilt.
Aspergillus genus is a key component in fermentation and food processing. However, sterigmatocystin (STE)—a mycotoxin produced by several species of Aspergillus—limits the use of some Aspergillus ...species (such as Aspergillus versicolor, Aspergillus inflatus, and Aspergillus parasiticus) because of its toxicity and carcinogenicity. Here, we engineered an STE‐free Aspergillus versicolor strain based on genome mining techniques. We sequenced and assembled the Aspergillus versicolor D5 genome (34.52 Mb), in which we identified 16 scaffolds and 54 biosynthetic gene clusters (BGCs). We silenced cytochrome P450 coding genes STC17 and STC27 by insertional inactivation. The production of STE in the Δstc17 mutant strain was increased by 282% but no STE was detected in the Δstc27 mutant. Metabolites of Δstc27 mutant exhibited growth‐promoting effect on plants. Our study makes significant progress in improving the application of some Aspergillus strains by restricting their production of toxic and carcinogenic compounds.
The genome of A. versicolor D5 is 34.52 Mb and consists of 54 biosynthetic gene clusters. Sterigmatocystin production can be suppressed by silencing the P450‐coding gene STC27. The sterigmatocystin‐free Δstc27 mutant strain has the activity of promoting plant growth, in contrast to the inhibiting effect of the wild strain D5.
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