Sasa argenteostriata - A potential plant for phytostabilization remediation of lead-zinc tailing-contaminated soil.

Phytoremediation is an effective way to remediate metal-contaminated soils. During phytoremediation, plants immobilize heavy metals through the roots to reduce the mobility, toxicity and dispersal of the metals, and the changes in the activity of the roots are often accompanied by changes in the rhizosphere ecosystems, in which rhizobacteria are essential components and interact with roots to maintain the stability of the rhizosphere ecosystem and improve soil health. In this study, the phytoremediation potential of Sasa argenteostriata (Regel) E.G. Camu and the response of rhizobacteria were revealed with different levels of lead-zinc tailing contamination (Pb, Zn, and Cd concentrations of 1197.53, 3243.40, and 185.44 mg/kg for M1 and 2301.71, 6087.95, and 364.00 mg/kg for M2, respectively). The BCF of Sasa argenteostriata increased with increasing soil pollution, and the BCFPb, BCFZn, and BCFCd were 0.19, 0.27, and 0.08, respectively, under the M2 treatment; in contrast, the TF decreased with increasing soil pollution, and the TFPb, TFZn, and TFCd were 0.39, 0.85, and 0.07, respectively, under the M1 treatment. The mobility of Pb in the rhizosphere was higher than that of Zn and Cd, and the percentage of residual (Res) Zn and Cd in the rhizosphere increased, while the acid-soluble (Aci) Pb was significantly higher, leading to obvious uptake of Pb by the roots. Correlation analysis showed that Sasa argenteostriata affected the rhizobacterial community by changing the rhizosphere soil pH, the contents of organic matter and NRFM, and bacteria such as Proteobacteria and MND1, which are highly resistant to heavy metals (HMs), became the dominant species in the community. Further PICRUSt2 analysis showed that reducing metal transport across the membranes and increasing the efficiency of cellular reproduction were the main metabolic mechanisms of bacterial tolerance to HMs. Overall, the roots of Sasa argenteostriata were able to immobilize more heavy metals in PbZn tailing-contaminated soil, reducing the toxicity of HMs in the soil, and then influencing the rhizobacteria to change the community structure and metabolism mechanism to adapt to the HM-contaminated environment, and the soil fertility was increased, which together promoted the health and stability of the soil. This study is the first to illustrate the phytoremediation potential and response of the rhizobacterial community of Sasa argenteostriata under multimetal contamination of PbZn tailings. The results of the study provide some guidance for the practice of lead-zinc tailing-phytoremediation and soil health.

Effects of Low-Light Environments on the Growth and Physiological and Biochemical Parameters of Indocalamus and Seasonal Variations in Leaf Active Substance Contents.

Indocalamus, characterized by its expansive leaves, low height, strong reproductive capacity, and abundant bioactive compounds, has extensive utility in the realms of food processing, the manufacturing of packaging materials, and the advancement of novel pharmaceuticals. Two light environments, CK (100% full light) and ST (50% full light), were established to explore the effects of low-light environments on the reproductive ability, morphological characteristics, photosynthetic properties, and leaf active substances of 14 Indocalamus species. The findings revealed that in comparison to the CK treatment, for 14 species of Indocalamus under the ST treatment, (1) the diameter, single leaf area, and leaf area index increased by 8.27%, 8.14%, and 17.88%, respectively; (2) the net photosynthetic rate decreased by 15.14%, and the total chlorophyll contents increased by 20.25%; and (3) the total flavonoid contents increased by 18.28% in autumn, the total polyphenol contents increased by 48.96% in spring, and the total polysaccharide contents increased by 31.44% and 30.81% in summer and winter, respectively. In summary, Indocalamus are adapted to survive in low-light environments; the growth and physiological indices differ significantly between the two light environments, and the low-light environment can effectively promote the growth and development of the leaves. Furthermore, the leaves are rich in flavonoids, polyphenols, polysaccharides, and active substances, which are affected by the light intensity and the season to varying degrees, and autumn and winter are the best times for harvesting the leaves. The leaves of I. hunanensis and I. lacunosus are richest in flavonoids and polyphenols, while the leaves of I. kunmingensis cv. fuminer are richest in polysaccharides. The main findings of this study demonstrate that Indocalamus has strong shade tolerance and tremendous leaf value, laying the foundation for broadening the application of their leaves and for their industrial development in understory composite planting systems.

Effects of Linpan nature therapy on health benefits in older women with and without hypertension.

Background: Nature therapy can significantly benefit the physiology and psychology of middle-aged and older people, but previous studies have focused on forest environments. The restoration potential of rural environments in urban fringe areas, which are more accessible to older people on a daily basis, has not been fully studied. This study assessed the effects of nature therapy on the physical and mental health of older women in a rural setting (locally known as Linpan) in the urban fringe area of Chengdu, China. Methods: We recruited a total of 60 older women (65.3 ± 5.5 years old) living in cities for 3 days of nature therapy in the winter (30 subjects) and spring (30 subjects), including 20 hypertensive patients. Results: The results showed that the overall blood pressure, pulse and sleep dysfunction rating scores of the participants were significantly lower than the pretest levels, and the finger blood oxygen saturation, mid-day salivary alpha-amylase and cortisol were increased post-treatment. Increases in these biomarker indicates and increase in stress. There were significant differences in the changes in systolic blood pressure between the hypertension group (HTN) and the normal group (normal) (HTN decreased by 8.8%, normal decreased by 5.4%), salivary alpha-amylase content (HTN decreased by 0.3%, normal increased by 16.9%), and sleep dysfunction rating scores (HTN decreased by 59.6%, normal decreased by 54%). The decreases in systolic blood pressure and pulse in the winter group were higher than those in the spring group by 1.8 and 4.4%, respectively, while the increases in salivary alpha-amylase content and salivary cortisol content were lower than those in the spring group by 11.7 and 11.2%, respectively, and the decrease in sleep dysfunction rating scores was lower than that in the spring group by 7.1%. Conclusion: Our study concluded that nature therapy based on various health activities in the Linpan has significant health effects on older women. It can regulate blood pressure and pulse in older women, relieve cardiovascular disease, improve sleep quality. Meanwhile, older women with high blood pressure experienced a more significant effect than the healthy group.

The role of miR1 and miR133a in new-onset atrial fibrillation after acute myocardial infarction.

BACKGROUND: The development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is a clinical complication that requires a better understanding of the causative risk factors. This study aimed to explore the risk factors and the expression and function of miR-1 and miR-133a in new atrial fibrillation after AMI. METHODS: We collected clinical data from 172 patients with AMI treated with emergency percutaneous coronary intervention (PCI) between October 2021 and October 2022. Independent predictors of NOAF were determined using binary logistic univariate and multivariate regression analyses. The predictive value of NOAF was assessed using the area under the receiver operating characteristic (ROC) curve for related risk factors. In total, 172 venous blood samples were collected preoperatively and on the first day postoperatively; the expression levels of miR-1 and miR-133a were determined using the polymerase chain reaction. The clinical significance of miR-1 and miR-133a expression levels was determined by Spearman correlation analysis. RESULTS: The Glasgow prognostic score, left atrial diameter, and infarct area were significant independent risk factors for NOAF after AMI. We observed that the expression levels of miR-1 and miR-133a were significantly higher in the NOAF group than in the non-NOAF group. On postoperative day 1, strong associations were found between miR-133a expression levels and the neutrophil ratio and between miR-1 expression levels and an increased left atrial diameter. CONCLUSIONS: Our findings indicate that the mechanism of NOAF after AMI may include an inflammatory response associated with an increased miR-1-related mechanism. Conversely, miR-133a could play a protective role in this clinical condition.

A Suboptimal Optimizing Strategy for Velocity Vector Estimation in Single-Observer Passive Localization.

In a single-observer passive localization system, the velocity and position of the target are estimated simultaneously. However, this can lead to correlated errors and distortion of the estimated value, making independent estimation of the speed and position necessary. In this study, we introduce a novel optimization strategy, suboptimal estimation, for independently estimating the velocity vector in single-observer passive localization. The suboptimal estimation strategy converts the estimation of the velocity vector into a search for the global optimal solution by dynamically weighting multiple optimization criteria from the starting point in the solution space. Simulation verification is conducted using uniform motion and constant acceleration models. The results demonstrate that the proposed method converges faster with higher accuracy and strong robustness.

Effects of Simultaneous Application of Double Chelating Agents to Pb-Contaminated Soil on the Phytoremediation Efficiency of Indocalamus decorus Q. H. Dai and the Soil Environment.

Recent studies have shown that the combined application of ethylenediaminetetraacetic acid (EDTA) and degradable chelating agents can enhance EDTA's affinity for heavy metals and reduce its toxicity, but the effect of this combination on the phytoremediation remains largely unknown. This study evaluated and compared the effects of EDTA, nitrilotriacetic acid (NTA), and glutamic acid-N,N-diacetic acid (GLDA) alone (E, N, G treatment), and in combination (EN and EG treatment), on the growth of dwarf bamboo (Indocalamus decorus Q. H. Dai), their phytoremediation efficiency, and the soil environment in Pb-contaminated soil. The results showed that treatment E significantly reduced the biomass, while treatments N and EN were more conducive to the distribution of aerial plant biomass. Except for treatment E, the total Pb accumulation in all treatments increased significantly, with the highest increase in treatment EN. For double chelating agents, the acid-soluble Pb concentrations in rhizosphere and non-rhizosphere soils of treatments EN and EG were lower than those of treatment E, and the soil water-soluble Pb content after 20 days of treatment EN was significantly lower than that of treatment EG. Furthermore, chelating agents generally increased soil-enzyme activity in rhizosphere soil, indicating that chelating agents may promote plant heavy-metal uptake by changing the rhizosphere environment. In conclusion, treatment EN had the highest phytoremediation efficiency and significantly lower environmental risk than treatments E and EG, highlighting its massive potential for application in phytoremediation of Pb-contaminated soil when combined with I. decorus.

Elevated procalcitonin levels in the absence of infection in procalcitonin-secretin hepatocellular carcinoma: A case report.

BACKGROUND: Serum procalcitonin (PCT) is widely used to diagnose bacterial infection and sepsis. However, PCT may be elevated in some neoplasms. It is important to distinguish infection from no infection in such neoplasms. The relationship between hepatocellular carcinoma (HCC) and PCT is unknown. CASE SUMMARY: A 62-year-old male was admitted due to a hepatic lesion of unknown origin. The patient had an elevated PCT level. Infectious diseases were excluded after appropriate examination. He then underwent exploratory laparotomy and a left lateral hepatectomy was performed. The patient recovered with an uneventful postoperative course and PCT level decreased gradually and was normal on day 16. HCC was diagnosed by histopathology and no evidence of infection was observed. Furthermore, immunohistochemical analyses revealed that tumor cells were positive for PCT. CONCLUSION: HCC cells can secrete PCT in the absence of infection and PCT may be used as a marker to monitor the efficacy of tumor therapy.

Tolerance and Heavy Metal Accumulation Characteristics of Sasa argenteostriata (Regel) E.G. Camus under Zinc Single Stress and Combined Lead-Zinc Stress.

Sasa argenteostriata (Regel) E.G. Camus is a gramineous plant with the potential for phytoremediation. In this study, we aimed to determine its tolerance to zinc stress and combined lead-zinc stress and the effect of zinc on its absorption and accumulation characteristics of lead. The results showed that S. argenteostriata had good tolerance to zinc stress, and S. argenteostriata was not significantly damaged when the zinc stress concentration was 600 mg/L. Under both zinc stress and combined lead-zinc stress, the root was the main organ that accumulated heavy metals in S. argenteostriata. The presence of zinc promoted the absorption of lead by the root of S. argenteostriata, and the lead content in the root under PZ1, PZ2, PZ3 and PZ4 treatments was 2.15, 4.31, 4.47 and 6.01 times that of PZ0 on the 20 days. In the combined lead-zinc stress treatments, the toxicity of heavy metals to S. argenteostriata was mainly caused by lead. Under high concentrations of combined lead-zinc stress (PZ4), the proportion of zinc in the leaf of S. argenteostriata on the 20 days increased, which was used as a tolerance strategy to alleviate the toxicity of lead.

Efficiency of heterogeneous chelating agents on the phytoremediation potential and growth of Sasa argenteostriata (Regel) E.G. Camus on Pb-contaminated soil.

Ethylenediaminetetraacetic acid (EDTA) is one of the most effective chelating agents for enhancing lead (Pb) accumulation in various plant organs. However, it has a higher risk of causing secondary pollution than other chelating agents. To reduce such environmental risks and increase remediation efficiency, EDTA can be combined with degradable chelating agents for use in phytoremediation, but there are few reports on the combination of EDTA and nitrilotriacetic acid (NTA). This study evaluated the effects of combined EDTA and NTA application at different concentrations (900, 1200, or 1500 mg/kg) and with different methods (1 application or 3 applications) on dwarf bamboo (Sasa argenteostriata (Regel) E.G. Camus) growth and phytoremediation efficiency and on the soil environment in pot experiments with Pb-contaminated soil. Applying EDTA and NTA together resulted in lower soil water-soluble Pb concentrations than applying EDTA alone and therefore resulted in lower environmental risk. The increased availability of soil Pb produced a stress response in the dwarf bamboo plants, which increased their biomass significantly. Moreover, under the chelating treatments, the soil Pb availability increased, which promoted Pb translocation in plants. The Pb content in the aerial parts of the dwarf bamboo increased significantly in all treatments (translocation factors increased by 300~1500% compared with that in CK). The Pb content increase in the aerial parts caused high proline accumulation in dwarf bamboo leaves, to alleviate Pb toxicity. Maximum Pb accumulation was observed in the EN1500 treatment, which was significantly higher than that in the other treatments except the EN900 treatment. This study elucidates the choice of remediation techniques and the physiological characteristics of the plants used in such studies. In conclusion, the EN900 treatment resulted in the lowest environmental risk, greatest biomass production, and highest phytoremediation efficiency of all treatments, indicating that it has great potential for application in phytoremediation with dwarf bamboo in Pb-contaminated soil.

Dynamic study of the lead (Pb) tolerance and accumulation characteristics of new dwarf bamboo in Pb-contaminated soil.

Dwarf bamboo is a woody plant with potential for use in the remediation of Pb-contaminated soil. Due to its clonal growth habit, there are two keys to its application for continuous soil Pb remediation: 1) its ability to form shoots and grow into new bamboo normally under Pb stress and 2) the Pb tolerance and accumulation characteristics of this new bamboo. Here, 5 species of dwarf bamboo were treated with 2 levels of soil Pb stress (0 and 1500 mg kg-1). In the roots of 3 of the species (Sasa argenteostriata, Sasaella glabra, and Indocalamus decorus), Pb tended to be distributed along the cell wall and transported to vacuoles. In the other 2 species (Sasa auricoma and Sasa fortunei), Pb was arranged linearly along the cell wall. Under Pb treatment, the new bamboo of all species showed gradual physiological adaptation to Pb stress. Correlations of the net photosynthetic rate, superoxide dismutase activity, and free proline levels with Pb content in new leaves in November were all higher than those in July, though that of malondialdehyde content decreased, suggesting that new dwarf bamboo exhibits good soil Pb stress tolerance. Sasa argenteostriata and Indocalamus decorus consistently maintained higher antioxidant enzyme activities and free proline levels than the other species under Pb treatment, and the total biomass per pot of the new bamboo decreased the least compared to that in the Pb-free treatment for these two species. Therefore, these bamboo species may be used in the long-term continuous remediation of Pb-contaminated soil.

Effects of Variations in Color and Organ of Color Expression in Urban Ornamental Bamboo Landscapes on the Physiological and Psychological Responses of College Students.

Visual characteristics (e.g., the color and shape) of ornamental plants can significantly affect their beneficial influence on humans. Prior research, however, has largely focused on the effects of the color or shape of flowers and the impact of differences in the visual appearance of foliage plants and plants with ornamental stalks has not yet been fully explored. This study examined the psychophysiological effects of urban ornamental bamboos that expressed different colors on different organs. Three hundred Chinese college students participated in the experiment. They were randomly assigned to view images of five ornamental bamboo landscapes with the following different visual characteristics: green stalks (GS) non-green stalks (NGS) multicolored stalks (MS) green leaves (GL) and multicolored leaves (ML). Before and after viewing the images, their EEG, blood pressure, pulse, profile of mood states (POMS) score, and state-trait anxiety inventory (STAI) score were measured. The results showed that ornamental bamboo landscapes have extremely significant beneficial psychophysiological effects as compared to urban landscapes. After viewing landscapes in the NGS and MS groups, EEG, blood pressure, and pulse rate of subjects showed more beneficial changes. Significant gender differences were observed only in systolic blood pressure and in the vigor score. In addition, an extremely significant interaction between color and organ of color expression was observed on systolic and diastolic blood pressure. Organ of expression had significant main effects on all the physiological indicators and the fatigue, vigor, and irritability scores, while color only had a main effect on systolic blood pressure. Our study concluded that viewing urban ornamental bamboo landscapes with different visual characteristics has different effects on humans. With regards to ornamental bamboo, the organ expressing the color had a greater impact on psychophysiological responses than did the type of color itself. These study results can provide guidance for landscape construction of urban greening.

Biomass allocation strategies and Pb-enrichment characteristics of six dwarf bamboos under soil Pb stress.

Dwarf bamboos are clonal plants with potential applications in the remediation of heavy metal-polluted soils, although their pollution adaptation strategies are unknown. This study examined the biomass allocation strategies and lead (Pb) enrichment characteristics of various dwarf bamboo tissues by the end of the growing season and explored their potential for phytoremediation of Pb stress in the soils. Six dwarf bamboo genotypes were treated with three levels (0, 300, and 1500 mg kg-1) of soil Pb stress. The majority of the bamboos adopted two biomass allocation strategies to adapt to Pb stress, namely, "reducing biomass allocation into new bamboo growth" and "increasing/stabilizing biomass allocation into rhizomes". Pb accumulation was highest in the roots, rhizomes, and old stems and showed the following trend: rhizomes/old stems> new roots/old roots> old leaves> new leaves> new stems among various tissues. Moreover, the six bamboos used three different Pb-enrichment strategies, as follows: (i) "rhizome domination and old stem synergy" (Sasaella glabra (Nakai) f. albo-striata Muroi, Sasa auricoma (Mitford) E.G. Camus, Sasa fortunei (Van Houtte) Fiori, and Shibataea lanceifolia C.H. Hu); (ii) "old stem domination and rhizome synergy" (Indocalamus decorus Q.H. Dai); and (iii) "old stem domination and new root synergy" (Sasa argenteostriata (Regel) E.G. Camus). In Pb-contaminated soils, genotypes with TFs greater than 1 were Sasa fortunei (Van Houtte) Fiori, Sasa argenteostriata (Regel) E.G. Camus, and Indocalamus decorus Q.H. Dai; in addition, only S. argenteostriata had BCF values greater than 1. Furthermore, this study provides the first evidence that S. argenteostriata can extract 0.22 and 0.58 mgplant-1 of Pb ions in soil polluted with 300 and 1500 mg kg-1 Pb, respectively. S. argenteostriata showed the greatest potential for phytoremediation among the bamboo genotypes in both Pb-contaminated urban and mining sites.

Physiological and Psychological Effects of Watching Videos of Different Durations Showing Urban Bamboo Forests with Varied Structures.

This study illustrated the physiological and psychological effects of watching videos of different durations showing bamboo forests with varied structures. Physiological indicators, including EEG (electroencephalogram), blood pressure, skin conductance, and pulse, were monitored in 180 Chinese university students (mean age: 20.72 ± 2.56 years) while they were watching bamboo videos. Before and after watching the videos, their psychological indicators, including positive and negative moods, were measured using the Profile of Mood States questionnaire. After watching the bamboo videos of different durations, all of the physiological indicators responded to the stimulation after only 1 min. The indicators showed different trends at 1, 3 and 5 min. EEG decreased and then was maintained at a stable level after 1 min, and the high ß, low ß, and α waves had no significant differences between 1, 3 and 5 min. Blood pressure dropped to a stable state after 3 min, and the decline was significantly different greater after 3 min than after 1 min. Skin conductance increased for 1 to 5 min, and it did not stabilize after a long time (5 min). Pulse decreased after 1 min but increased after 5 min. After watching the videos with bamboo of varying structures, the physiological and psychological indicators showed significantly different changes. Skin conductance significantly increased (mean value: 6.78%), and the amount of sweat was more effectively reduced, thereby reducing tension, when the students viewed videos of sympodial bamboo forests compared with monopodial bamboo forests. Bamboo forests with a higher canopy density (0.83-0.85) could significantly decrease α waves (mean value: 1.50 Hz), relaxing the human body. High ß and low ß waves showed greater decreases, with tension reduced more effectively, when bamboo forests with a low tilt ratio (< 1.5%) were viewed. Bamboo forests with neat undergrowth could have more beneficial physiological and psychological effects on the human body.

Different strategies for lead detoxification in dwarf bamboo tissues.

Dwarf bamboo Sasa argenteostriata (Regel) E.G. Camus is considered as potential plants for metal phytoremediation in previous filed observations. However, the mechanisms of lead (Pb) detoxification has not been described. The objective of this study was to explore the difference strategies or mechanisms of Pb detoxification in plant tissues. In this regard, four Pb treatments with hydroponics including 0 (control), 300, 600, and 900 mg L-1 were conducted to examine subcellular compartmentalization, Pb accumulation/species and antioxidant-assisted chelation. Our findings showed the retention of Pb by the whip-root system is one of its detoxification mechanisms to avoid damage the shoots. In addition, the cell wall retention is the dominant detoxification strategy of whips, new roots, old roots and new/old stems, while vacuolar compartmentalization is for new/old leaves. Interestingly, four low-mobility/-toxicity Pb species (i.e., FNaCl, FHAc, FHCl and FR) are distributed in roots, whips and stems, while two high-mobility/-toxicity Pb species (FE and FW) in leaves. The conversion of Pb to low-toxicity/-migration is a Pb-detoxification strategy in roots, whips and stems but not in leaves. Besides, the new/old roots and leaves can alleviate Pb damage through the synthesis of non-protein thiol, glutathione and phytochelatins. Among these, phytochelatins play a leading role in the detoxification in new/old roots, while glutathione is in new/old leaves. This study provides the first comprehensive evidence regarding the different strategies for Pb detoxification in dwarf bamboo tissues from physiological to cellular level, supporting that this plant could be rehabilitated for phytoremediation in Pb-contaminated media.

A negative feedback regulatory loop between miR-138 and TP53 is mediated by USP10.

TP53 is a critical tumor suppressor. In approximately 50% of human cancers the TP53 gene is either lost or mutated. The expression level of TP53 in the cells is tightly controlled by a fine-tune machinery, mainly through the Mdm2-mediated ubiquitination pathway. On the other side, the ubiquitinated TP53 could be reversed and stabilized by USP7 and USP10, to keep the amount of TP53 in check. MicroRNAs can negatively regulate TP53 expression levels through direct targeting or positively regulate TP53 function through the repression of negative regulators of TP53. Here we report that microRNA-138 controls TP53 expression by directly targeting USP10. Furthermore, TP53 represses microRNA-138 expression, forming a negative feedback regulatory loop. This finding adds another layer of complexity to the TP53 network.

EDTA-facilitated toxic tolerance, absorption and translocation and phytoremediation of lead by dwarf bamboos.

Bamboos are considered as potential plants for phytoremediation. However, the mechanisms of EDTA-assisted bamboo for lead (Pb) control has not been described. The objective of this study was to examine the tolerance and behaviors of Pb to screen bamboos for Pb-contaminated soil and to explore the effects of EDTA on their phytoremediation. In this regard, five dwarf bamboos were treated with various doses Pb (0-1500 mg kg-1) and/or EDTA (500 or 250-1000 mg kg-1) to investigate antioxidant systems and Pb accumulation/species. Our findings showed that different doses of Pb significantly affect lipid peroxidation and antioxidant compounds in studied bamboos. EDTA increased the absorption of soil Pb2+ in all tissues with increasing Pb doses, while the Pb concentrations in all bamboo roots was higher than those in other tissues. Among these plants, Arundinaria argenteostriata (AA) and A. fortunei (AF) showed greater oxidative tolerance than other bamboos. Moreover, Pb accumulation showed the highest values in AA and AF plants relative to other bamboos. With increasing EDTA doses, levels of reducible and residual Pb decreased but the weak acid-soluble and total Pb increased in Pb-stressed AA/AF soils. Similarly, EDTA increased Pb2+ concentration in both bamboo tissues, while the Pb2+ level in leaves was higher than that in other organs at the highest EDTA dose. This study provides the first comprehensive evidence regarding EDTA enhancing the availability, absorption, and translocation of Pb in bamboo/soil, suggesting the application of EDTA may be an effective strategy for phytoremediation with two Arundinaria bamboos in Pb-contaminated soils.

Friend or Foe: MicroRNAs in the p53 network.

The critical tumor suppressor gene TP53 is either lost or mutated in more than half of human cancers. As an important transcriptional regulator, p53 modulates the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress cancer development, microRNAs that are activated by gain-of-function mutant p53 confer oncogenic properties. On the other hand, the expression of p53 is tightly controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the TP53 gene directly or other factors in the p53 network so that expression and function of either the wild-type or the mutant forms of p53 is downregulated. Therefore, depending on the wild-type or mutant p53 context, microRNAs contribute substantially to suppress or exacerbate tumor development.

miR-130a Deregulates PTEN and Stimulates Tumor Growth.

H-RasV12 oncogene has been shown to promote autophagic cell death. Here, we provide evidence of a contextual role for H-RasV12 in cell death that is varied by its effects on miR-130a. In E1A-immortalized murine embryo fibroblasts, acute expression of H-RasV12 promoted apoptosis, but not autophagic cell death. miRNA screens in this system showed that miR-130a was strongly downregulated by H-RasV12 in this model system. Enforced expression of miR-130a increased cell proliferation in part via repression of PTEN. Consistent with this effect, miR-130a overexpression in human breast cancer cells promoted Akt phosphorylation, cell survival, and tumor growth. In clinical specimens of multiple human cancers, expression of miR-130 family members correlated inversely with PTEN expression. Overall, our results defined miR-130a as an oncogenic miRNA that targets PTEN to drive malignant cell survival and tumor growth. Cancer Res; 77(22); 6168-78. ©2017 AACR.

RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21.

Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. Overall survival rate was also significantly improved by FA-3WJ-LNA-miR21 RNP. These results are indicative of the clinical benefit of FA-3WJ RNP-based gene therapy for the successful targeted therapy of developing and even recurring glioblastoma.

ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5.

MicroRNAs (miRNA) are mostly downregulated in cancer. However, the mechanism underlying this phenomenon and the precise consequence in tumorigenesis remain obscure. Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. In liver cancer, the ERK-mediated XPO5 suppression reduces miR-122, increases microtubule dynamics, and results in tumor development and drug resistance. Analysis of clinical specimens further showed that XPO5 phosphorylation is associated with poor prognosis for liver cancer patients. Our study reveals a function of ERK in miRNA biogenesis and suggests that modulation of miRNA export has potential clinical implications.