Selection of the Dominant Endophytes Based on Illumina Sequencing Analysis for Controlling Bacterial Wilt of Patchouli Caused by Ralstonia solanacearum.

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.

A Semisynthesis Platform for the Efficient Production and Exploration of Didemnin-Based Drugs.

Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.

Physiological Characteristics and Transcriptomic Dissection in Two Root Segments with Contrasting Net Fluxes of Ammonium and Nitrate of Poplar Under Low Nitrogen Availability.

To investigate physiological and transcriptomic regulation mechanisms underlying the distinct net fluxes of NH4+ and NO3- in different root segments of Populus species under low nitrogen (N) conditions, we used saplings of Populus × canescens supplied with either 500 (normal N) or 50 (low N) µM NH4NO3. The net fluxes of NH4+ and NO3-, the concentrations of NH4+, amino acids and organic acids and the enzymatic activities of nitrite reductase (NiR) and glutamine synthetase (GS) in root segment II (SII, 35-70 mm to the apex) were lower than those in root segment I (SI, 0-35 mm to the apex). The net NH4+ influxes and the concentrations of organic acids were elevated, whereas the concentrations of NH4+ and NO3- and the activities of NiR and GS were reduced in SI and SII in response to low N. A number of genes were significantly differentially expressed in SII vs SI and in both segments grown under low vs normal N conditions, and these genes were mainly involved in the transport of NH4+ and NO3-, N metabolism and adenosine triphosphate synthesis. Moreover, the hub gene coexpression networks were dissected and correlated with N physiological processes in SI and SII under normal and low N conditions. These results suggest that the hub gene coexpression networks play pivotal roles in regulating N uptake and assimilation, amino acid metabolism and the levels of organic acids from the tricarboxylic acid cycle in the two root segments of poplars in acclimation to low N availability.

Genome-Wide Identification and Characterization of the NF-YA Gene Family and Its Expression in Response to Different Nitrogen Forms in Populus × canescens.

The NF-YA gene family is a class of conserved transcription factors that play important roles in plant growth and development and the response to abiotic stress. Poplar is a model organism for studying the rapid growth of woody plants that need to consume many nutrients. However, studies on the response of the NF-YA gene family to nitrogen in woody plants are limited. In this study, we conducted a systematic and comprehensive bioinformatic analysis of the NF-YA gene family based on Populus × canescens genomic data. A total of 13 PcNF-YA genes were identified and mapped to 6 chromosomes. According to the amino acid sequence characteristics and genetic structure of the NF-YA domains, the PcNF-YAs were divided into five clades. Gene duplication analysis revealed five pairs of replicated fragments and one pair of tandem duplicates in 13 PcNF-YA genes. The PcNF-YA gene promoter region is rich in different cis-acting regulatory elements, among which MYB and MYC elements are the most abundant. Among the 13 PcNF-YA genes, 9 contained binding sites for P. × canescens miR169s. In addition, RT-qPCR data from the roots, wood, leaves and bark of P. × canescens showed different spatial expression profiles of PcNF-YA genes. Transcriptome data and RT-qPCR analysis showed that the expression of PcNF-YA genes was altered by treatment with different nitrogen forms. Furthermore, the functions of PcNF-YA genes in transgenic poplar were analyzed, and the potential roles of PcNF-YA genes in the response of poplar roots to different nitrogen forms were revealed, indicating that these genes regulate root growth and development.

PcNRAMP1 Enhances Cadmium Uptake and Accumulation in Populus × canescens.

Poplars are proposed for the phytoremediation of heavy metal (HM) polluted soil. Characterization of genes involved in HM uptake and accumulation in poplars is crucial for improving the phytoremediation efficiency. Here, Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) encoding a transporter involved in cadmium (Cd) uptake and transport was functionally characterized in Populus × canescens. Eight putative PcNRAMPs were identified in the poplar genome and most of them were primarily expressed in the roots. The expression of PcNRAMP1 was induced in Cd-exposed roots and it encoded a plasma membrane-localized protein. PcNRAMP1 showed transport activity for Cd2+ when expressed in yeast. The PcNRAMP1-overexpressed poplars enhanced net Cd2+ influxes by 39-52% in the roots and Cd accumulation by 25-29% in aerial parts compared to the wildtype (WT). However, Cd-induced biomass decreases were similar between the transgenics and WT. Further analysis displayed that the two amino acid residues of PcNRAMP1, i.e., M236 and P405, play pivotal roles in regulating its transport activity for Cd2+. These results suggest that PcNRAMP1 is a plasma membrane-localized transporter involved in Cd uptake and transporting Cd from the roots to aerial tissues, and that the conserved residues in PcNRAMP1 are essential for its Cd transport activity in poplars.

Dissecting MicroRNA-mRNA Regulatory Networks Underlying Sulfur Assimilation and Cadmium Accumulation in Poplar Leaves.

The process of cadmium (Cd) accumulation and detoxification under different sulfur levels remains largely unknown in woody plants. To investigate the physiological and transcriptomic regulation mechanisms of poplars in response to different sulfate (S) supply levels and Cd exposure, we exposed Populus deltoides saplings to one of the low, moderate and high S levels together with either 0 or 50 µM Cd. Cd accumulation was decreased in low S-treated poplar leaves, and it tended to be increased in high S-supplied leaves under the Cd exposure condition. Sulfur nutrition was deficient in low S-supplied poplars, and it was improved in high S-treated leaves. Cd exposure resulted in lower sulfur level in the leaves supplied with moderate S, it exacerbated a Cd-induced sulfur decrease in low S-treated leaves and it caused a higher sulfur concentration in high S-supplied leaves. In line with the physiological changes, a number of mRNAs and microRNAs (miRNAs) involved in Cd accumulation and sulfur assimilation were identified and the miRNA-mRNA networks were dissected. In the networks, miR395 and miR399 members were identified as hub miRNAs and their targets were ATP sulfurylase 3 (ATPS3) and phosphate 2 (PHO2), respectively. These results suggest that Cd accumulation and sulfur assimilation are constrained by low and enhanced by high S supply, and Cd toxicity is aggravated by low and relieved by high S in poplar leaves, and that miRNA-mRNA regulatory networks play pivotal roles in sulfur-mediated Cd accumulation and detoxification in Cd-exposed poplars.

Competing Endogenous RNA Networks Underlying Anatomical and Physiological Characteristics of Poplar Wood in Acclimation to Low Nitrogen Availability.

Although poplar plantations are often established on nitrogen (N)-poor soil, the physiological and molecular mechanisms underlying wood properties of poplars in acclimation to low N availability remain largely unknown. To investigate wood properties of poplars in acclimation to low N, Populus � canescens saplings were exposed to either 50 (low N) or 500 (normal N) �M NH4NO3 for 2 months. Low N resulted in decreased xylem width and cell layers of the xylem (the number of cells counted along the ray parenchyma on the stem cross section), narrower lumina of vessels and fibers, greater thickness of double fiber walls (the walls between two adjacent fiber cells), more hemicellulose and lignin deposition, and reduced cellulose accumulation in poplar wood. Consistently, concentrations of gibberellins involved in cell size determination and the abundance of various metabolites including amino acids, carbohydrates and precursors for cell wall biosynthesis were decreased in low N-supplied wood. In line with these anatomical and physiological changes, a number of mRNAs, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) were significantly differentially expressed. Competing endogenous RNA regulatory networks were identified in the wood of low N-treated poplars. Overall, these results indicate that miRNAs-lncRNAs-mRNAs networks are involved in regulating wood properties and physiological processes of poplars in acclimation to low N availability.

Physiological and molecular mechanisms of heavy metal accumulation in nonmycorrhizal versus mycorrhizal plants.

Uptake, translocation, detoxification, and sequestration of heavy metals (HMs) are key processes in plants to deal with excess amounts of HM. Under natural conditions, plant roots often establish ecto- and/or arbuscular-mycorrhizae with their fungal partners, thereby altering HM accumulation in host plants. This review considers the progress in understanding the physiological and molecular mechanisms involved in HM accumulation in nonmycorrhizal versus mycorrhizal plants. In nonmycorrhizal plants, HM ions in the cells can be detoxified with the aid of several chelators. Furthermore, HMs can be sequestered in cell walls, vacuoles, and the Golgi apparatus of plants. The uptake and translocation of HMs are mediated by members of ZIPs, NRAMPs, and HMAs, and HM detoxification and sequestration are mainly modulated by members of ABCs and MTPs in nonmycorrhizal plants. Mycorrhizal-induced changes in HM accumulation in plants are mainly due to HM sequestration by fungal partners and improvements in the nutritional and antioxidative status of host plants. Furthermore, mycorrhizal fungi can trigger the differential expression of genes involved in HM accumulation in both partners. Understanding the molecular mechanisms that underlie HM accumulation in mycorrhizal plants is crucial for the utilization of fungi and their host plants to remediate HM-contaminated soils.

Physiological and transcriptional regulation in poplar roots and leaves during acclimation to high temperature and drought.

To elucidate the physiological and transcriptional regulatory mechanisms that underlie the responses of poplars to high temperature (HT) and/or drought in woody plants, we exposed Populus alba × Populus tremula var. glandulosa saplings to ambient temperature (AT) or HT under 80 or 40% field capacities (FC), or no watering. HT increased the foliar total carbon (C) concentrations, and foliar δ(13) C and δ(18) O. HT triggered heat stress signaling via increasing levels of abscisic acid (ABA) and indole-3-acetic acid (IAA) in poplar roots and leaves. After perception of HT, poplars initiated osmotic adjustment by increasing foliar sucrose and root galactose levels. In agreement with the HT-induced heat stress and the changes in the levels of ABA and carbohydrates, we detected increased transcript levels of HSP18 and HSP21, as well as NCED3 in the roots and leaves, and the sugar transporter gene STP14 in the roots. Compared with AT, drought induced greater enhancement of foliar δ(13) C and δ(18) O in poplars at HT. Similarly, drought caused greater stimulation of the ABA and foliar glucose levels in poplars at HT than at AT. Correspondingly, desiccation led to greater increases in the mRNA levels of HSP18, HSP21, NCED3, STP14 and INT1 in poplar roots at HT than at AT. These results suggest that HT has detrimental effects on physiological processes and it induces the transcriptional regulation of key genes involved in heat stress responses, ABA biosynthesis and sugar transport and HT can cause greater changes in drought-induced physiological and transcriptional responses in poplar roots and leaves.

Exogenous abscisic acid alleviates zinc uptake and accumulation in Populus × canescens exposed to excess zinc.

A greenhouse experiment was conducted to study whether exogenous abscisic acid (ABA) mediates the responses of poplars to excess zinc (Zn). Populus × canescens seedlings were treated with either basal or excess Zn levels and either 0 or 10 µm ABA. Excess Zn led to reduced photosynthetic rates, increased Zn accumulation, induced foliar ABA and salicylic acid (SA), decreased foliar gibberellin (GA3 ) and auxin (IAA), elevated root H2 O2 levels, and increased root ratios of glutathione (GSH) to GSSG and foliar ratios of ascorbate (ASC) to dehydroascorbate (DHA) in poplars. While exogenous ABA decreased foliar Zn concentrations with 7 d treatments, it increased levels of endogenous ABA, GA3 and SA in roots, and resulted in highly increased foliar ASC accumulation and ratios of ASC to DHA. The transcript levels of several genes involved in Zn uptake and detoxification, such as yellow stripe-like family protein 2 (YSL2) and plant cadmium resistance protein 2 (PCR2), were enhanced in poplar roots by excess Zn but repressed by exogenous ABA application. These results suggest that exogenous ABA can decrease Zn concentrations in P. × canescens under excess Zn for 7 d, likely by modulating the transcript levels of key genes involved in Zn uptake and detoxification.

Exploring the Biosynthetic Potential of Tistrella Species for Producing Didemnin Antitumor Agents.

Didemnins are a class of cyclic depsipeptides derived from sea tunicates that exhibit potent anticancer, antiviral, and immunosuppressive properties. Although certain Tistrella species can produce didemnins, their complete biosynthetic potential remains largely unexplored. In this study, we utilize feature-based molecular networking to analyze the metabolomics of Tistrella mobilis and Tistrella bauzanensis, focusing on the production of didemnin natural products. In addition to didemnin B, we identify nordidemnin B and [hysp2]didemnin B, as well as several minor didemnin analogs. Heterologous expression of the didemnin biosynthetic gene cluster in a Streptomyces host results in the production of only didemnin B and nordidemnin B in limited quantities. Isotope-labeling studies reveal that the substrate promiscuity of the adenylation domains during biosynthesis leads to the accumulation of nordidemnin B and [hysp2]didemnin B. Additionally, precursor-directed biosynthesis is applied to generate eight novel didemnin derivatives by supplementing the culture with structurally related amino acids. Furthermore, we increased the titers of nordidemnin B and [hysp2]didemnin B by supplementing the fermentation medium with l-valine and l-isoleucine, respectively. Finally, both compounds undergo side-chain oxidation to enhance their biological activity, with their anticancer properties found to be as potent as plitidepsin.

The root-associated Fusarium isolated based on fungal community analysis improves phytoremediation efficiency of Ricinus communis L. in multi metal-contaminated soils.

Phytoremediation is a widely accepted bioremediation method of treating heavy metal contaminated soils. Nevertheless, the remediation efficiency in multi-metal contaminated soils is still unsatisfactory attributable to susceptibility to different metals. To isolate root-associated fungi for improving phytoremediation efficiency in multi-metal contaminated soils, the fungal flora in root endosphere, rhizoplane, rhizosphere of Ricinus communis L. in heavy metal contaminated soils and non-heavy metal contaminated soils were compared by ITS amplicon sequencing, and then the critical fungal strains were isolated and inoculated into host plants to improve phytoremediation efficiency in Cd, Pb, and Zn-contaminated soils. The fungal ITS amplicon sequencing analysis indicated that the fungal community in root endosphere was more susceptible to heavy metals than those in rhizoplane and rhizosphere soils and Fusarium dominated the endophytic fungal community of R. communis L. roots under heavy metal stress. Three endophytic strains (Fusarium sp. F2, Fusarium sp. F8, and Fusarium sp. F14) isolated from Ricinus communis L. roots showed high resistances to multi-metals and possessed growth-promoting characteristics. Biomass and metal extraction amount of R. communis L. with Fusarium sp. F2, Fusarium sp. F8, and Fusarium sp. F14 inoculation in Cd-, Pb- and Zn-contaminated soils were significantly higher than those without the inoculation. The results suggested that fungal community analysis-guided isolation could be employed to obtain desired root-associated fungi for enhancing phytoremediation of multi-metal contaminated soils.

Homolog of Human placenta-specific gene 8, PcPLAC8-10, enhances cadmium uptake by Populus roots.

Cadmium (Cd) pollution of soil occurs worldwide. Phytoremediation is an effective approach for cleaning up Cd polluted soil. Fast growing Populus species with high Cd uptake capacities are desirable for phytoremediation. Thus, it is important to elucidate the molecular functions of genes involved in Cd uptake by poplars. In this study, PcPLAC8-10, a homolog of Human placenta-specific gene 8 (PLAC8) implicated in Cd transport was functionally characterized in Populus × canescens. PcPLAC8-10 was transcriptionally induced in Cd-treated roots and it encoded a plasma membrane-localized transporter. PcPLAC8-10 exhibited Cd uptake activity when expressed in yeast cells. No difference in growth was observed between wild type (WT) and PcPLAC8-10-overexpressing poplars. PcPLAC8-10-overexpressing poplars exhibited increases in net Cd2+ influxes by 192% and Cd accumulation by 57% in the roots. However, similar reductions in biomass were found in WT and transgenic poplars when exposed to Cd. The complete motif of CCXXXXCPC in PcPLAC8-10 was essential for its Cd transport activity. These results suggest that PcPLAC8-10 is a plasma membrane-localized transporter responsible for Cd uptake in the roots and the complete CCXXXXCPC motif of PcPLAC8-10 plays a key role in its Cd transport activity in poplars.

A novel analytical model of solute transport in a layered aquifer system with mixing processes in the reservoirs.

Analytical models of solute transport have been widely used to aid the understanding of the physical and chemical processes undergone by substances introduced in a layered aquifer system. However, in previous studies, the advection component of transport was assumed to be one dimensional, while also ignoring the mixing processes that occur in the inlet and the outlet reservoirs. In this study, new sets of models describing those mixing processes are presented. Beyond that, these models were integrated into already existing models and the result is a novel analytical model of solute transport in aquifer-aquitard systems. The novel analytical solution was derived by the Laplace transform method and the finite-cosine Fourier transform method under the mobile-immobile (MIM) framework. The calculations take into account: the longitudinal and vertical dispersion, the molecular diffusion and the horizonal and vertical advection components of solute transport, as well as first-order chemical reaction, in both the aquifer and the aquitard. A finite-difference solution of the model is tested against experimental data in order to critique its reliability. Results indicate that the numerical and analytical solutions of the new model match well with experimental data. This new model outperforms the previous models in terms of interpreting experimental data. The mixing old and new water in the reservoirs during solute transport in aquifer-aquitard systems is important. Global sensitivity analysis demonstrates that the output concentration of solute in the aquifer-aquitard system is most sensitive to the volume of water in the inlet reservoir. The contribution of the molecular diffusion effect to the total mass flux of the tracer cross the aquifer-aquitard interface is much smaller than the contribution of the dispersive and advective effects.

Identification and Functional Prediction of Poplar Root circRNAs Involved in Treatment With Different Forms of Nitrogen.

Circular RNAs (circRNAs) are a class of noncoding RNA molecules with ring structures formed by covalent bonds and are commonly present in organisms, playing an important regulatory role in plant growth and development. However, the mechanism of circRNAs in poplar root responses to different forms of nitrogen (N) is still unclear. In this study, high-throughput sequencing was used to identify and predict the function of circRNAs in the roots of poplar exposed to three N forms [1 mM NO3 - (T1), 0.5 mM NH4NO3 (T2, control) and 1 mM NH4 + (T3)]. A total of 2,193 circRNAs were identified, and 37, 24 and 45 differentially expressed circRNAs (DECs) were screened in the T1-T2, T3-T2 and T1-T3 comparisons, respectively. In addition, 30 DECs could act as miRNA sponges, and several of them could bind miRNA family members that play key roles in response to different N forms, indicating their important functions in response to N and plant growth and development. Furthermore, we generated a competing endogenous RNA (ceRNA) regulatory network in poplar roots treated with three N forms. DECs could participate in responses to N in poplar roots through the ceRNA regulatory network, which mainly included N metabolism, amino acid metabolism and synthesis, response to NO3 - or NH4 + and remobilization of N. Together, these results provide new insights into the potential role of circRNAs in poplar root responses to different N forms.

Sulfur metabolism, organic acid accumulation and phytohormone regulation are crucial physiological processes modulating the different tolerance to Pb stress of two contrasting poplars.

To investigate the pivotal physiological processes modulating lead (Pb) tolerance capacities of poplars, the saplings of two contrasting poplar species, Populus × canescens with high Pb sensitivity and Populus nigra with relatively low Pb sensitivity, were treated with either 0 or 8 mM Pb for 6 weeks. Lead was absorbed by the roots and accumulated massively in the roots and leaves, leading to overproduction of reactive oxygen species, reduced photosynthesis and biomass in both poplar species. Particularly, the tolerance index of P. × canescens was significantly lower than that of P. nigra. Moreover, the physiological responses including the concentrations of nutrient elements, thiols, organic acids, phytohormones and nonenzymatic antioxidants, and the activities of antioxidative enzymes in the roots and leaves were different between the two poplar species. Notably, the differences in concentrations of nutrient elements, organic acids and phytohormones were remarkable between the two poplar species. A further evaluation of the Pb tolerance-related physiological processes showed that the change of 'sulfur (S) metabolism' in the roots was greater, and that of 'organic acid accumulation' in the roots and 'phytohormone regulation' in the leaves were markedly smaller in P. × canescens than those in P. nigra. These results suggest that there are differences in Pb tolerance capacities between P. × canescens and P. nigra, which is probably associated with their contrasting physiological responses to Pb stress, and that S metabolism, organic acid accumulation and phytohormone regulation are probably the key physiological processes modulating the different Pb tolerance capacities between the two poplar species.

Lead exposure-induced defense responses result in low lead translocation from the roots to aerial tissues of two contrasting poplar species.

To explore whether lead (Pb)-induced defense responses are responsible for the low root-to-shoot Pb translocation, we exposed saplings of the two contrasting poplar species, Populus × canescens with relatively high root-to-shoot Pb translocation and P. nigra with low Pb translocation, to 0 or 8 mM PbCl2. Pb translocation from the roots to aboveground tissues was lower by 57% in P. nigra than that in P. × canescens. Lower Pb concentrations in the roots and aerial tissues, greater root biomass, and lower ROS overproduction in the roots were found in P. nigra than those in P. × canescens treated with Pb. P. nigra roots had higher proportions of cell walls (CWs)-bound Pb and water insoluble Pb compounds, and higher transcript levels of some pivotal genes related to Pb vacuolar sequestration, such as phytochelatin synthetase 1.1 (PCS1.1), ATP-binding cassette transporter C1.1 (ABCC1.1) and ABCC3.1 than P. × canescens roots. Pb exposure induced defense responses including increases in the contents of pectin and hemicellulose, and elevated oxalic acid accumulation, and the transcriptional upregulation of PCS1.1, ABCC1.1 and ABCC3.1 in the roots of P. nigra and P. × canescens. These results suggest that the stronger defense barriers in P. nigra roots are probably associated with the lower Pb translocation from the roots to aerial tissues, and that Pb exposure-induced defense responses can enhance the barriers against Pb translocation in poplar roots.

Exosomal Non-Coding RNAs: Regulatory and Therapeutic Target of Hepatocellular Carcinoma.

Exosomes are small extracellular vesicles secreted by most somatic cells, which can carry a variety of biologically active substances to participate in intercellular communication and regulate the pathophysiological process of recipient cells. Recent studies have confirmed that non-coding RNAs (ncRNAs) carried by tumor cell/non-tumor cell-derived exosomes have the function of regulating the cancerous derivation of target cells and remodeling the tumor microenvironment (TME). In addition, due to the unique low immunogenicity and high stability, exosomes can be used as natural vehicles for the delivery of therapeutic ncRNAs in vivo. This article aims to review the potential regulatory mechanism and the therapeutic value of exosomal ncRNAs in hepatocellular carcinoma (HCC), in order to provide promising targets for early diagnosis and precise therapy of HCC.

LncRNA DiGeorge syndrome critical region gene 5: A crucial regulator in malignant tumors.

Long non-coding RNA (lncRNA), a subgroup of ncRNA with a length of more than 200 nt without protein coding function, has been recognized by the academia for its mediating effects of dysregulated expression on the tumorigenesis and development of a variety of tumors. LncRNA DiGeorge syndrome critical region gene 5 (DGCR5), originally found to induce DiGeorge syndrome, has been confirmed to be extremely dysregulated in multiple tumors, which mediates the malignant phenotypes of hepatocellular carcinoma, pancreatic cancer, lung cancer, etc. through the regulation of Wnt/ß-catenin, MEK/ERK1/2 and other cancerous signaling pathways as a molecular sponge. Researches on the cancerous derivation-related pathways involved in DGCR5 can provide potential molecular intervention targets for tumor precision treatment. Moreover, liquid biopsy based on the detection of DGCR5 in body fluids is also expected to provide a non-invasive evaluation method for the early diagnosis and prognostic evaluation of malignant tumors.

Exosomes in hepatocellular carcinoma microenvironment and their potential clinical application value.

Hepatocellular carcinoma (HCC) has become a challenging disease in the world today. Due to the limitations on the current diagnosis and treatment as well as its high metastatic ability and high recurrence rate, HCC gradually becomes the second deadliest tumor. Exosomes are one of the types of cell-derived vesicles and can carry intracellular materials such as genetic materials, lipids, and proteins. In recent years, it has been verified that exosomes are linked to numerous physiological and pathological processes, including HCC. However, how exosomes affect HCC progression remains largely unknown. In this review, the exosome-mediated cellular material transfer between cells of different types in the HCC microenvironment and their effects on the behaviors and functions of recipient cells are studied. Furthermore, we also addressed the underlying molecular mechanisms. We believe that new light on the diagnosis of this cancer as well as its treatment strategies will be shed after a collation of literature in this area.