Changes in soil stoichiometry, soil organic carbon mineralization and bacterial community assembly processes across soil profiles.

Soil organic carbon (SOC) mineralization is essential to biogeochemical recycling in terrestrial ecosystem. However, the microbial mechanisms underlying the nutrient-induced SOC mineralization remain uncertain. Here, we investigated how SOC mineralization was linked to microbial assembly processes as well as soil nutrient availability and stoichiometric ratio in a paddy rice ecosystem at four soil profile levels. Our results showed a sharp decrease in SOC mineralization from topsoil (112.61-146.34 mg CO2 kg-1 day-1) to subsoil (33.51-61.41 mg CO2 kg-1 day-1). High-throughput sequencing showed that both abundance and diversity of specialist microorganisms (Chao1: 1244.30-1341.35) significantly increased along the soil profile, while the generalist microorganisms (Chao1: 427.67-616.15; Shannon: 7.46-7.97) showed the opposite trend. Correspondingly, the proportion of deterministic processes that regulate specialist (9.64-21.59 %) and generalist microorganisms (21.17-53.53 %) increased and decreased from topsoil to subsoil, respectively. Linear regression modeling and partial least squares path modeling indicated that SOC mineralization was primarily controlled by the assembly processes of specialist microorganisms, which was significantly mediated by available soil C:N:P stoichiometry. This study highlighted the importance of soil stoichiometry-mediated bacterial community assembly processes in regulating SOC mineralization. Our results have an important implication for the integration of bacterial community assembly processes into the prediction of SOC dynamics.

The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer.

The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator. Biochemical studies reveal that tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpressed in small cell lung cancer (SCLC). Here, we explore the possibility that CARM1 methylation of NFIB is important for its transforming activity. Using a SCLC mouse model, we show that both CARM1 and the CARM1 methylation site on NFIB are critical for the rapid onset of SCLC. Furthermore, CARM1 and methylated NFIB are responsible for maintaining similar open chromatin states in tumors. Together, these findings suggest that CARM1 might be a therapeutic target for SCLC.

Regional Inequalities and Influencing Factors of Residents' Health in China: Analysis from the Perspective of Opening-Up.

While opening-up promotes regional economic development, its impact on the residents' health level cannot be ignored. Based on provincial data of China from 2009 to 2020, the Gini Coefficient and Theil Index are used to analyze the regional inequalities in residents' health in China. The Difference-in-Difference model is constructed to study the impact of China's opening-up policies and other factors on residents' health. The results show that, firstly, the health levels of Chinese residents have steadily improved and regional inequalities have been gradually narrowing. Secondly, the Belt and Road Initiative has significantly improved the residents' health along the route, while the Pilot Free Trade Zone, which is another important opening-up policy in China, has had an inhibitory effect on the health of residents. Thirdly, it is proven that the Belt and Road Initiative improves the health of residents in provinces along the route by increasing the degree of opening-up and improving the regional environmental quality. This study will support and advance the UN's Sustainable Development Goals (SDGs), especially SDG3 (Good Health and Well-being) and SDG10 (Reduced Inequalities).

Using Potential Molecular Transformation To Understand the Molecular Trade-Offs in Soil Dissolved Organic Matter.

Understanding the chemical composition and molecular transformation in soil dissolved organic matter (DOM) is important to the global carbon cycle. To address this issue, ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was applied to investigate DOM molecules in 36 paddy soils collected from subtropical China. All the detected 7576 unique molecules were divided into seven compound groups, and nine trade-off relationships between different compound groups were revealed based on principal component analysis and Pearson's correlation. An optimized method was developed to evaluate all potential molecular transformations in DOM samples. The concept of thermodynamics was introduced to evaluate the identified molecular transformations and classify them as thermodynamically favorable (TFP) and thermodynamically limited (TLP) processes. Here, we first tried to understand the molecular trade-offs by using the potential molecular transformations. All the nine trade-offs could be explained by molecular transformations. Six trade-offs had bases of biochemical reactions, and the trade-off-related direct transformations could explain the content variations of carbohydrate-like, condensed aromatic-like, tannin-like, and lignin-like compounds in TLP. More reasonable explanations existed in the TLP rather than TFP, which demonstrated the critical role of external energy in the molecular transformation of soil DOM.

SPINDOC binds PARP1 to facilitate PARylation.

SPINDOC is tightly associated with the histone H3K4me3 effector protein SPIN1. To gain a better understanding of the biological roles of SPINDOC, we identified its interacting proteins. Unexpectedly, SPINDOC forms two mutually exclusive protein complexes, one with SPIN1 and the other with PARP1. Consistent with its ability to directly interact with PARP1, SPINDOC expression is induced by DNA damage, likely by KLF4, and recruited to DNA lesions with dynamics that follows PARP1. In SPINDOC knockout cells, the levels of PARylation are reduced, in both the absence and presence of DNA damage. The SPINDOC/PARP1 interaction promotes the clearance of PARP1 from damaged DNA, and also impacts the expression of known transcriptional targets of PARP1. To address the in vivo roles of SPINDOC in PARP1 regulation, we generate SPINDOC knockout mice, which are viable, but slightly smaller than their wildtype counterparts. The KO mice display reduced levels of PARylation and, like PARP1 KO mice, are hypersensitive to IR-induced DNA damage. The findings identify a SPIN1-independent role for SPINDOC in the regulation of PARP1-mediated PARylation and the DNA damage response.

Genetic evidence for partial redundancy between the arginine methyltransferases CARM1 and PRMT6.

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders.

The aberrant expression of protein arginine methyltransferase 5 (PRMT5) has been associated with multiple cancers. Using the proteolysis targeting chimera technology, we discovered a first-in-class PRMT5 degrader 15 (MS4322). Here, we report the design, synthesis, and characterization of compound 15 and two structurally similar controls 17 (MS4370) and 21 (MS4369), with impaired binding to the von Hippel-Lindau E3 ligase and PRMT5, respectively. Compound 15, but not 17 and 21, effectively reduced the PRMT5 protein level in MCF-7 cells. Our mechanism studies indicate that compound 15 degraded PRMT5 in an E3 ligase- and proteasome-dependent manner. Compound 15 also effectively reduced the PRMT5 protein level and inhibited growth in multiple cancer cell lines. Moreover, compound 15 was highly selective for PRMT5 in a global proteomic study and exhibited good plasma exposure in mice. Collectively, compound 15 and its two controls 17 and 21 are valuable chemical tools for exploring the PRMT5 functions in health and disease.

Detecting Coal Pulverizing System Anomaly Using a Gated Recurrent Unit and Clustering.

The coal pulverizing system is an important auxiliary system in thermal power generation systems. The working condition of a coal pulverizing system may directly affect the safety and economy of power generation. Prognostics and health management is an effective approach to ensure the reliability of coal pulverizing systems. As the coal pulverizing system is a typical dynamic and nonlinear high-dimensional system, it is difficult to construct accurate mathematical models used for anomaly detection. In this paper, a novel data-driven integrated framework for anomaly detection of the coal pulverizing system is proposed. A neural network model based on gated recurrent unit (GRU) networks, a type of recurrent neural network (RNN), is constructed to describe the temporal characteristics of high-dimensional data and predict the system condition value. Then, aiming at the prediction error, a novel unsupervised clustering algorithm for anomaly detection is proposed. The proposed framework is validated by a real case study from an industrial coal pulverizing system. The results show that the proposed framework can detect the anomaly successfully.

CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300-mutated lymphomas.

Somatic mutations affecting CREBBP and EP300 are a hallmark of diffuse large B-cell lymphoma (DLBCL). These mutations are frequently monoallelic, within the histone acetyltransferase (HAT) domain and usually mutually exclusive, suggesting that they might affect a common pathway, and their residual WT expression is required for cell survival. Using in vitro and in vivo models, we found that inhibition of CARM1 activity (CARM1i) slows DLBCL growth, and that the levels of sensitivity are positively correlated with the CREBBP/EP300 mutation load. Conversely, treatment of DLBCLs that do not have CREBBP/EP300 mutations with CARM1i and a CBP/p300 inhibitor revealed a strong synergistic effect. Our mechanistic data show that CARM1i further reduces the HAT activity of CBP genome wide and downregulates CBP-target genes in DLBCL cells, resulting in a synthetic lethality that leverages the mutational status of CREBBP/EP300 as a biomarker for the use of small-molecule inhibitors of CARM1 in DLBCL and other cancers.

A randomized controlled trial of a nurse-led education pathway for asthmatic children from outpatient to home.

BACKGROUND: Education for asthmatic children in the outpatient department is insufficient. AIM: To evaluate the efficacy of a nurse-led education pathway, a standard education programme, on children with asthma. METHODS: One hundred and eighty participants enrolled and were randomly assigned to either the control group or the intervention group. The intervention group received predetermined step-by-step education sessions based on the self-designed education pathway, while the control group received usual care. Asthma control, health-related quality of life, and health-care utilization measures were taken at baseline and at follow-up visits between February 2016 and May 2018. RESULTS: Significantly higher scores for health-related quality of life and inhaler technique at the third-month visit and asthma control test at the sixth-month visit were seen in the intervention group. The numbers of unscheduled physician visits and school absences were lower in the intervention group than in the control group within 6 months. However, no significant differences were observed in emergency department visits and hospitalizations. CONCLUSION: The nurse-led education pathway could be considered effective for children with asthma visiting the outpatient department.

The effect of goal setting in asthma self-management education: A systematic review.

BACKGROUND: Asthma self-management education combining with behavior therapy is considered to be more effective. Goal setting is a common behavior change technique used to help patients self-manage their symptoms. However, empirical evidence around its effectiveness on asthma management lacks clarity. AIMS: To systematically integrate and appraise the evidence for effectiveness of goal setting interventions on asthma outcomes. METHODS: Databases included CENTRAL, PubMed, EMBASE, CINAHL and Proquest Psychology Database were systematically searched for relevant intervention studies employing goal setting technique as a method in asthma education program for self-management. Characteristic of studies and outcomes in clinical, psychosocial and healthcare utilization outcome were extracted. RESULTS: From a total of 2641 citations, 45 full-text articles were assessed for eligibility and 9 studies met the inclusion criteria. Eight studies were randomized controlled trial and one was before-after study. None studies have a high methodological quality. Goal-setting based intervention appeared to improve symptom control, quality of life and self-efficacy in adult patients with asthma. CONCLUSION: This systematic review highlighted the potential of a goal setting technique in the asthma self-management education. However, due to the limitations of the quality and quantity of the included literature, more rigorous studies are needed. In the future, better effective study protocol combining with goal setting approach and other behavior technique is needed to further investigate.

PRMT1 loss sensitizes cells to PRMT5 inhibition.

PRMT5 is an arginine methyltransferase that accounts for the vast majority of the symmetric methylation in cells. PRMT5 exerts its function when complexed with MEP50/WDR77. This activity is often elevated in cancer cells and correlates with poor prognosis, making PRMT5 a therapeutic target. To investigate the PRMT5 signaling pathway and to identify genes whose loss-of-function sensitizes cancer cells to PRMT5 inhibition, we performed a CRISPR/Cas9 genetic screen in the presence of a PRMT5 inhibitor. We identified known components of the PRMT5 writer/reader pathway including PRMT5 itself, MEP50/WDR77, PPP4C, SMNDC1 and SRSF3. Interestingly, loss of PRMT1, the major asymmetric arginine methyltransferase, also sensitizes cells to PRMT5 inhibition. We investigated the interplay between PRMT5 and PRMT1, and found that combinatorial inhibitor treatment of small cell lung cancer and pancreatic cancer cell models have a synergistic effect. Furthermore, MTAP-deleted cells, which harbor an attenuated PRMT5-MEP50 signaling pathway, are generally more sensitive to PRMT1 inhibition. Together, these findings demonstrate that there is a degree of redundancy between the PRMT5 and PRMT1 pathways, even though these two enzymes deposit different types of arginine methylation marks. Targeting this redundancy provides a vulnerability for tumors carrying a co-deletion of MTAP and the adjacent CDKN2A tumor suppressor gene.

The positive feedback loop between ILF3 and lncRNA ILF3-AS1 promotes melanoma proliferation, migration, and invasion.

PURPOSE: In our previous study, we identified that lncRNA ILF3 antisense RNA 1 (ILF3-AS1) is increased and has oncogenic roles in melanoma. However, the cause of the upregulation of ILF3-AS1 and the modulation between ILF3-AS1 and ILF3 in melanoma are still unknown. This study aimed to investigate the significances of the interaction between ILF3-AS1 and ILF3 in melanoma. MATERIALS AND METHODS: The expression of ILF3 in melanoma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR). The interactions between ILF3-AS1 and ILF3 were explored by the RNA immunoprecipitation assay, the transcription inhibition assay, qRT-PCR, the chromatin immunoprecipitation assay, and Western blot. Gain-of-function and loss-of-function assays were performed to investigate the effects of ILF3 and ILF3-AS1 on melanoma proliferation, migration, and invasion. RESULTS: ILF3 is also increased in melanoma tissues and cell lines. Increased expression of ILF3 predicts poor survival of melanoma patients. Mechanistic investigation revealed that ILF3 directly binds ILF3-AS1, increases ILF3-AS1 transcript stability, and upregulates ILF3-AS1 transcript levels. ILF3-AS1 represses the binding of EZH2 to the promoter of ILF3, induces euchromatin formation at ILF3 promoter, and activates ILF3 transcription. Thus, ILF3 and ILF3-AS1 form positive feedback loop, which induces the upregulation of ILF3 and ILF3-AS1 in melanoma. The expression of ILF3-AS1 is positively correlated with ILF3 in melanoma tissues. Functional assays revealed that overexpression of ILF3 promotes melanoma proliferation, migration, and invasion. Depletion of ILF3 inhibits melanoma proliferation, migration, and invasion. Moreover, concurrent depletion of ILF3 and ILF3-AS1 significantly suppresses melanoma proliferation, migration, and invasion. CONCLUSION: Both ILF3-AS1 and ILF3 are increased in melanoma. ILF3-AS1 and ILF3 positively regulate each other. Concurrent targeting ILF3-AS1 and ILF3 has significant tumor-suppressive roles in melanoma. Our data suggested that targeting the positive feedback loop between ILF3 and ILF3-AS1 may be promising therapeutic strategies for melanoma.

Predictive accuracy of the Braden Q Scale in risk assessment for paediatric pressure ulcer: A meta-analysis.

AIMS: Paediatric pressure ulcers are a serious problem to healthcare service. Thus, effective and early identification of the risk of developing pressure ulcer is essential. The Braden Q scale is a widely used tool in the risk assessment of paediatric pressure ulcer, but its predictive power is controversial. Hence, we performed a meta-analysis to evaluate the predictive power of the Braden Q scale for pressure ulcer in hospitalised children and offer recommendations for clinical decision. METHODS: Studies that evaluated the predictive power of the Braden Q scale were searched through databases in English and Chinese, including Medline, Cochrane Library, Embase, CINAHL, SinoMed, CNKI, Wangfang and VIP. The studies were screened by two independent reviewers. QUADAS-2 was used to assess the risk of bias of eligible studies. Demographic data and predictive value indices were extracted. The pooled sensitivity, specificity and receiver operating characteristics (ROC) were calculated by MetaDiSc 1.4 using random-effects models. RESULTS: Cochran Q = 26.13 (P = 0.0036) indicated the existence of heterogeneity; the I2 for pooled DOR was 61.7%, suggesting significant heterogeneity among the included studies. The pooled sensitivity and specificity were 0.73 (95% CI: 0.67-0.78) and 0.61 (95% CI: 0. 59-0.63), respectively, yielding a combined DOR of 3.47 (95% CI: 2-6.01). The area under the ROC curve was 0.7078 ± 0.0421, and the overall diagnostic accuracy (Q*) was 0.6591 ± 0.0337. Sensitivity analysis showed the results were robust. CONCLUSION: The Braden Q scale has moderate predictive validity with medium sensitivity and low specificity for pressure ulcers in hospitalised children. Further development and modification of this tool for use in paediatric population are warranted.

Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma.

Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.

Comparing the Curative Efficacy of Different Skin Grafting Methods for Third-Degree Burn Wounds.

BACKGROUND Our research purpose was to compare the curative efficacy of different skin grafting methods for treating third-degree burn wounds. MATERIAL AND METHODS A total of 105 patients with third-degree burns were involved in this study. The burn wounds of these patients were treated using three different methods: Meek skin grafting, Stamp skin grafting, and Microskin grafting. Patients treated with different methods were placed in different groups. The skin graft survival rate, skin graft fusion time, wound healing time, total time of surgery, and 1% total body surface area (TBSA) treatment costs in each group were evaluated during and after the grafting procedures. After the operations, patients were followed up for 3 to 18 months in order to evaluate the postoperative outcomes. RESULTS The skin graft survival rate was significantly higher in the Meek group compared to the rates in the Stamp and Microskin groups (both P<0.01). In addition, the skin graft fusion time, wound healing time, and 1% TBSA treatment costs were significantly lower in the Meek group compared to those in the Stamp and Microskin groups (both P<0.01). Furthermore, the Meek group exhibited better results with respect to curative efficacy, scarring status, and joint activity in comparison to the other two groups (both P<0.05). CONCLUSIONS The Meek skin grafting method showed better clinical efficacy for treating large wound areas in third-degree burn patients compared to the Stamp and Microskin skin grafting methods.

Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine-Arginine-Rich Protein ASF/SF2.

Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes. In this study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin T1-depedent genes at the transcription level. We further found that a cis-element on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2. Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which contributes to the control of the subsequent transcription events. J. Cell. Biochem. 118: 4020-4032, 2017. © 2017 Wiley Periodicals, Inc.

Long Noncoding RNA PVT1 as a Novel Diagnostic Biomarker and Therapeutic Target for Melanoma.

Accumulating evidences indicated that plasmacytoma variant translocation 1 (PVT1) plays vital roles in several cancers. However, the expression, functions, and clinical values of PVT1 in melanoma are still unknown. In this study we measured the expression of PVT1 in clinical tissues and serum samples and explored the diagnostic value of PVT1 for melanoma and the effects of PVT1 on melanoma cell proliferation, cell cycle, and migration. Our results, combined with publicly available PVT1 expression data, revealed that PVT1 is upregulated in melanoma tissues compared with nonneoplastic nevi tissues. Serum PVT1 level is significantly increased in melanoma patients compared with age and gender-matched nonmelanoma controls with melanocytic nevus. Receiver operating characteristic curve analyses revealed that serum PVT1 level could sensitively discriminate melanoma patients from controls. Furthermore, serum PVT1 level indicted melanoma dynamics. Functional experiments showed that overexpression of PVT1 promotes melanoma cells proliferation, cell cycle progression, and migration, while depletion of PVT1 significantly inhibits melanoma cells proliferation, cell cycle progression, and migration. Collectively, our results indicate that PVT1 functions as an oncogene in melanoma and could be a potential diagnostic biomarker and therapeutic target for melanoma.

Effects of miR-145-5p through NRAS on the cell proliferation, apoptosis, migration, and invasion in melanoma by inhibiting MAPK and PI3K/AKT pathways.

We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS. After transfecting miR-145-5p mimics, miR-145-5p inhibitors, NRAS cDNA and NRAS siRNA into CHL-1, VMM917 and SK-mel-28 cells, functional assays were used to detect the proliferation, apoptosis, invasion and migration, including MTT, flow cytometry, Transwell and wound healing assays. In addition, xenograft models in nude mice were also conducted to verify the role of miR-145-5p in vivo. MiR-145-5p was able to suppress proliferation, invasion, and migration of VMM917 and CHL-1 cells and induce apoptosis by inhibiting MAPK and PI3K/AKT pathways. However, aberrant expression of miR-145-5p and NRAS has little impact on the viability and metastasis of BRAF-mutant melanoma. The higher expression of miR-145-5p in xenograft models repressed the VMM917-induced and CHL-1-induced tumor growth observably and has little effect on SK-mel-28-induced tumor growth which was consistent with the results in vitro. Through targeting NRAS, miR-145-5p could suppress cell proliferation, invasion, and migration and induce apoptosis of CHL-1 and VMM917 melanoma cells by inhibiting MAPK and PI3K/AKT pathways.

Long noncoding RNA MHENCR promotes melanoma progression via regulating miR-425/489-mediated PI3K-Akt pathway.

Increasing evidences demonstrated that long noncoding RNAs (lncRNAs) are frequently dysregulated and have critical roles in many tumors. However, the roles and functional mechanisms of lncRNAs in melanoma remain largely unknown. In this study, we identified a novel lncRNA MHENCR which was upregulated in melanoma tissues and further upregulated in metastatic melanoma. Increased expression of MHENCR indicted poor survival of melanoma patients. Functional experiments revealed that MHENCR knockdown significantly inhibited melanoma cells proliferation, induced cell cycle arrest and apoptosis, and also attenuated melanoma cells migration in vitro. Furthermore, we identified MHENCR as a competitively endogenous RNA, which specifically bound to miR-425 and miR-489, upregulated their target genes IGF1 and SPIN1 expression, and further activated PI3K-Akt pathway. Statistically significant correlations were observed between MHENCR expression and IGF1 and SPIN1 in melanoma tissues. In vivo functional experiments further confirmed the pro-growth and pro-metastasis roles of MHENCR. Collectively, our findings revealed that MHENCR functions as an oncogene in melanoma via activating miR-425/489-mediated PI3K-Akt pathway, and may be a therapeutic target for melanoma.