miR-129-5p and -3p co-target WWP1 to suppress gastric cancer proliferation and migration.

Gastric cancer (GC) is a worldwide health problem. Uncovering the underlining molecular mechanisms of GC is of vital significance. Here, we identified a novel oncogene WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in GC. WWP1 could promote GC cell proliferation and migration in vitro and expedite GC growth in vivo. We also found out two microRNAs (miRNAs): miR-129-5p and -3p could both target WWP1. Interestingly, miR-129-5p bound to the CDS region of WWP1 mRNA. The miR-129 pairs (miR-129-5p and -3p) play pivotal roles in GC to suppress its proliferation and migration in vitro and slow down GC growth in vivo by repressing WWP1. In summary, we identified two tumor suppressive miRNAs which share the same precursor that could regulate the same oncogene WWP1 in GC. Our finding would add new route for GC research and treatment.

The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a severe health problem worldwide. Clarifying the mechanisms for the deregulation of oncogenes and tumour suppressors in CRC is vital for its diagnosis, treatment, prognosis and prevention. Hu antigen R (HuR), which is highly upregulated in CRC, functions as a pivotal oncogene to promote CRC progression. However, the underlying cause of its dysregulation is poorly understood. METHODS: In CRC tissue sample pairs, HuR protein levels were measured by Western blot and immunohistochemical (IHC) staining, respectively. HuR mRNA levels were also monitored by qRT-PCR. Combining meta-analysis and microRNA (miRNA) target prediction software, we predicted miRNAs that targeted HuR. Pull-down assay, Western blot and luciferase assay were utilized to demonstrate the direct binding of miR-22 on HuR's 3'-UTR. The biological effects of HuR and miR-22 were investigated both in vitro by CCK-8, EdU and Transwell assays and in vivo by a xenograft mice model. JASPAR and SABiosciences were used to predict transcriptional factors that could affect miR-22. Luciferase assay was used to explore the validity of putative Jun binding sites for miR-22 regulation. ChIP assay was performed to test the Jun's occupancy on the C17orf91 promoter. RESULTS: We observed a significant upregulation of HuR in CRC tissue pairs and confirmed the oncogenic function of HuR both in vitro and in vivo. We found that an important tumour-suppressive miRNA, miR-22, was significantly downregulated in CRC tissues and inversely correlated with HuR in both CRC tissues and CRC cell lines. We demonstrated that miR-22 directly bound to the 3'-UTR of HuR and led to inhibition of HuR protein, which repressed CRC proliferation and migration in vitro and decelerated CRC xenografted tumour growth in vivo. Furthermore, we found that the onco-transcription factor Jun could inhibit the transcription of miR-22. CONCLUSIONS: Our findings highlight the critical roles of the Jun/miR-22/HuR regulatory axis in CRC progression and may provide attractive potential targets for CRC prevention and treatment.

Effects of dietary taurine on growth, non-specific immunity, anti-oxidative properties and gut immunity in the Chinese mitten crab Eriocheir sinensis.

Taurine has been widely researched as a growth-promoting additive or as an antioxidant in aquatic animals because of its multiple functions, however, few studies have explored its effects on crustacean in spite of the occurrence of serious diseases. We studied the effects of taurine supplementation on the growth, non-specific immunity, anti-oxidative properties and gut immunity of the Chinese mitten crab Eriocheir sinensis. Healthy crabs (8.0 ±â€¯0.5 g) were fed diets supplemented with taurine at 0% (control), 0.2%, 0.4%, 0.8%, and 1.6% for 65 days. At the end of this 65 days feeding trial, the final weight, weight gain, specific growth rate, and feed conversion ratio were best in crabs fed the 0.4% taurine diet, followed by that in those fed the 0.8% taurine diet; the parameters were worst for the control group. Carapace length (CL) and carapace width (CW) were significantly increased in the crab fed the 0.4% and 0.8% taurine diet than that of the other three groups. Total haemocyte count (THC) and acid phosphatase (ACP) activity were significantly higher in the crab fed the 0.8% taurine diet than in those belonging to the other groups, the crabs fed the 0.4% taurine diet had the highest phenoloxidase (PO), lysozyme (LZM), and alkaline phosphatase (AKP) activities, however, there was no obvious change in their haemocyanin (Hc) content. According to superoxide dismutase (SOD), glutathione Peroxidase (GSH-PX), total anti-oxidant capacity (T-AOC) activities and malondialdehyde (MDA) content, the antioxidant capacity was significantly induced by taurine diet, while was higher in crabs fed 0.4 %-0.8% taurine diet than that of the other groups. Taurine supplementation significantly up-regulated the expression of gut immune genes (EsToll2, EsRelish) and antimicrobial peptides (EsALF1, EsALF2, EsCrus1, EsCrus2) in crabs gut fed the 0.2-0.8% taurine diet group compared to control. Thus, these study results indicate that dietary taurine is important for improving growth, regulating immunity, and enhancing the antioxidant capacity in crabs, with the recommended optimum dietary allowance being 0.4 %-0.8% taurine for E. sinensis.

miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1.

BACKGROUND: Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated. METHODS: In CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model. RESULTS: In colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3'-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1. CONCLUSIONS: This study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.

LDLR promotes autophagy-mediated cisplatin resistance in ovarian cancer associated with the PI3K/AKT/mTOR signaling pathway.

Autophagy is one of the underlying causes of resistance to many antitumor drugs, including cisplatin (DDP). The low-density lipoprotein receptor (LDLR) is a regulator of ovarian cancer (OC) progression. However, whether LDLR regulates DDP resistance in OC via autophagy-related pathways remains unclear. LDLR expression was measured by quantitative real-time PCR, western blot (WB) and IHC staining. A Cell Counting Kit 8 assay was employed to evaluate DDP resistance and cell viability, and flow cytometry was used to assess apoptosis. WB analysis was employed to evaluate the expression of autophagy-related proteins and PI3K/AKT/mTOR signaling pathway proteins. The autophagolysosomes and the fluorescence intensity of LC3 were observed by transmission electron microscopy and immunofluorescence staining, respectively. A xenograft tumor model was established to explore the role of LDLR in vivo. LDLR was highly expressed in OC cells, which was correlated with disease progression. In DDP-resistant OC cells, high LDLR expression was related to DDP resistance and autophagy. Downregulation of LDLR repressed autophagy and growth in DDP-resistant OC cell lines by activating the PI3K/AKT/mTOR pathway, and these effects were eliminated by an mTOR inhibitor. In addition, LDLR knockdown also reduced OC tumor growth by suppressing autophagy associated with the PI3K/AKT/mTOR pathway. LDLR promoted autophagy-mediated DDP resistance in OC associated with the PI3K/AKT/mTOR pathway, indicating that LDLR might be a new target to prevent DDP resistance in OC patients.

Oncogenic KRAS signaling drives evasion of innate immune surveillance in lung adenocarcinoma by activating CD47.

KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.

A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers.

Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRASG12C mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo. CRISPR/Cas9-mediated knockout of Rason in mouse embryonic fibroblasts inhibits KRAS-mediated tumor transformation. Genetic deletion of Rason abolishes oncogenic KRAS-driven pancreatic and lung cancer tumorigenesis in LSL-KrasG12D; Trp53R172H/+ mice. Mechanistically, RASON directly binds to KRASG12D/V and inhibits both intrinsic and GTPase activating protein (GAP)-mediated GTP hydrolysis, thus sustaining KRASG12D/V in the GTP-bound hyperactive state. Therapeutically, deprivation of RASON sensitizes KRAS mutant pancreatic cancer cells and patient-derived organoids to EGFR inhibitors. Our findings identify RASON as a critical regulator of oncogenic KRAS signaling and a promising therapeutic target for KRAS mutant cancers.

Design, synthesis, and evaluation of 4(1H)-quinolinone and urea derivatives as KRASG12C inhibitors with potent antitumor activity against KRAS-mutant non-small cell lung cancer.

KRASG12C is the most prevalent KRAS mutation in non-small cell lung cancer (NSCLC) and has emerged as a promising therapeutic target. Herein, two series of novel 4(1H)-quinolinone and urea compounds were designed based on the reported KRASG12C inhibitor SH-9. Many compounds showed significantly growth inhibitory activity against human NSCLC cells with KRASG12C mutation in cell viability assays. Compound 20a exhibited an IC50 value of 0.5 µM in KRASG12C-mutant NCI-H358 cells with 21-fold selectivity over KRASWT NCI-H2228 cells. LC-MS analysis indicated that compounds 14c, 14h and 20a covalently bound to KRASG12C rather than KRASWT. Moreover, these compounds could remarkably trap KRASG12C in its inactive state by blocking SOS1-mediated GDP/GTP exchange. Furthermore, treatment of NCI-H358 but not NCI-H2228 cells with 20a dose-dependently reduced the phosphorylation of KRAS downstream effectors ERK and AKT. Importantly, 20a significantly inhibited tumor growth in NCI-H358 xenograft models by suppressing KRASG12C signalling. These results indicate that 20a is a promising candidate worthy of further investigation.

Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) and CD74 emerge as important players in pathogenesis and angiogenesis of several types of malignant tumors. The purpose of this study was to evaluate the expression of MIF and CD74 in cervical squamous cell carcinoma and explore the potential roles they play in cervical tumor angiogenesis. METHODS: Macrophage migration inhibitory factor and CD74 expression was assessed by immunohistochemistry in 209 cases with various degrees of cervical epithelial lesions, including 40 normal cervical epithelia, 43 mild cervical intraepithelial neoplasia 1 (CIN 1), 41 moderate-severe cervical intraepithelial neoplasia (CIN 2 to 3), and 85 cervical squamous cell carcinomas (SCCs). CD34 staining was used for counting microvessel density. Semiquantitative reverse transcription polymerase chain reaction and Western blot were used to detect messenger RNA and protein levels of MIF and CD74 in normal and malignant cervical tissues and cervical cancer cell lines SiHa and C-33A. The concentration of vascular endothelial growth factor (VEGF) in the conditioned media of cervical cancer cells was analyzed by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemical analysis showed that MIF and CD74 expression was significantly higher in CIN than in the normal samples and higher in SCC than in CIN. The overexpression of MIF was correlated with deep stromal infiltration but not with the other clinicopathologic features of SCC. Correlation analyses revealed that MIF was positively related to CD74, and both protein levels were associated with microvessel density. Exogenous MIF induced VEGF secretion in SiHa and C-33A cells in a dose-dependent manner, which can be inhibited by MIF-specific inhibitor (ISO-1) or anti-CD74 antibody. CONCLUSION: Overexpression of MIF and CD74 in SCC and its precancerous lesions and the up-regulation of VEGF secretion in cervical cancer cells indicate that MIF and CD74 may play critical roles in the pathogenesis and angiogenesis of cervical cancer.

LINC00035 Transcriptional Regulation of SLC16A3 via CEBPB Affects Glycolysis and Cell Apoptosis in Ovarian Cancer.

OBJECTIVE: Ovarian cancer (OC) represents the most lethal gynecologic malignancy globally. Over the decades, lncRNAs have been considered as study focuses due to their genome-wide expression through multiple mechanisms in which regulation of target gene transcription through interaction with transcription factors or epigenetic proteins is proven. In the present work, we focus on the functional role of LINC00035 in OC and its regulation mechanism on gene expression. METHODS: We collected OC tissues and adjacent tumor-free tissues surgically resected from 67 OC patients. Cultured human OC cell lines SKOV3 and A2780 were assayed for their viability, migration, invasion, apoptosis in vitro using CCK-8 assays, transwell assays, and flow cytometric analysis. OC cell tumorigenesis in vivo was evaluated by mouse xenograft experiments. Glycolysis was evaluated by glucose uptake, lactate release, and ATP production assays. Luciferase activity assay, RNA immunoprecipitation (RIP), and RNA pull-down were performed to confirm the interactions among LINC00035, CEBPB, and SLC16A3. RESULTS: LINC00035 was upregulated in OC tissues. LINC00035 knockdown was shown to repress SKOV3 and A2780 cell viability, migration, invasion, induce their apoptosis, and reduce glucose uptake, lactate release, and ATP production. LINC00035 could recruit CEBPB into the SLC16A3 promoter region, thus increasing the SLC16A3 transcription. SLC16A3 was upregulated in OC tissues. SLC16A3 knockdown exerted similar effects on SKOV3 and A2780 cells as LINC00035 knockdown. Rescue experiments found SLC16A3 overexpression resisting to LINC00035 knockdown on SKOV3 and A2780 cell viability, migration, invasion, apoptosis, glucose uptake, lactate release, and ATP production. Results also showed LINC00035 knockdown could inhibit OC cell tumorigenesis in vivo. CONCLUSION: The study reveals that LINC00035 promotes OC progression by regulating glycolysis and cell apoptosis through CEBPB-mediated transcriptional promotion of SLC16A3.

Effects of Notch signaling components from breast cancer cells treated in culture with resveratrol.

Resveratrol (Res) has an anti-tumor effect. Notch signaling components from breast cancer cells treated in culture with Resveratrol was investigated. MDA-MB-231cells were divided into control group (Res-untreated) and Res-treated groups including six concentrations 0 µM, 10 µM, 20 µM, 40 µM, 80 µM and 160 µM. Cytotoxicity test were evaluated by CCK-8. The mRNA and Protein expression levels of Notch1, Jagged1, Dll4 and Hes-5 were detected by RT-PCR and Western blot. The mRNA expression of Notch1, Jagged1, Hes-5 and Dll4 in the Res administration group decreased significantly (0.01 < p < .05), and Hes-5 and Dll4 were extremely significant (p < .01). Compared with the blank control group, the protein expression of Notch1 and Dll4 decreased significantly in each concentration Res group, but the decrease of protein expression of Jagged1 and Hes-5 was not significant. In conclusion, Res regulates mRNA and protein expression of Notch1, Dll4 of MDA-MB-231 cells via Notch pathway.

Prediction of Potential Associations Between miRNAs and Diseases Based on Matrix Decomposition.

It is known that miRNA plays an increasingly important role in many physiological processes. Disease-related miRNAs could be potential biomarkers for clinical diagnosis, prognosis, and treatment. Therefore, accurately inferring potential miRNAs related to diseases has become a hot topic in the bioinformatics community recently. In this study, we proposed a mathematical model based on matrix decomposition, named MFMDA, to identify potential miRNA-disease associations by integrating known miRNA and disease-related data, similarities between miRNAs and between diseases. We also compared MFMDA with some of the latest algorithms in several established miRNA disease databases. MFMDA reached an AUC of 0.9061 in the fivefold cross-validation. The experimental results show that MFMDA effectively infers novel miRNA-disease associations. In addition, we conducted case studies by applying MFMDA to three types of high-risk human cancers. While most predicted miRNAs are confirmed by external databases of experimental literature, we also identified a few novel disease-related miRNAs for further experimental validation.

Molecular mechanism of miR-204 regulates proliferation, apoptosis and autophagy of cervical cancer cells by targeting ATF2.

Objective: To investigate the regulatory mechanism of miR-204 on proliferation, apoptosis and autophagy of cervical cancer cells. Methods: The expression of miR-204 in cervical cancer tissues and cell lines was detected by real-time PCR. Cell viability and apoptosis were detected by MTT and flow cytometry, respectively. Protein expression of Bcl-2, Bax, Caspase-3 and LC3I/II in C33A cells after transfection was detected by Western blot assay. The interaction between miR-204 and ATF2 was verified by Targetscan online prediction, dual-luciferase assay and Western blot. Results: The expression of miR-204 was significantly down-regulated in cervical cancer tissues and cell lines (p < .05). Cell viability was suppressed while apoptosis was enhanced in C33A cells transfected with miR-204. In addition, overexpression of miR-204 reduced protein expression of Bcl-2 and LC3I/II and elevated protein expression of Bax and Caspase-3 in C33A cells (p < .05). The results of Targetscan online prediction, dual-luciferase assay and Western blot indicted that miR-204 could regulate the expression of ATF2. Cell viability was increased (p < .05) and the expression of ATF2 and LC3I/II was down-regulated (p < .05) in C33A cells after silencing of ATF2. Ectopic expression of ATF2 could restore miR-204 mediated inhibition on proliferation of C33A cells. Conclusions: miR-204 could inhibit proliferation and autophagy and induce apoptosis of cervical cancer cells by targeting ATF2, representing promising target for cervical cancer treatment.

Effect of dihydroartemisinin on epithelial-to-mesenchymal transition in canine mammary tumour cells.

Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties, generating metastases. Dihydroartemisinin (DHA) exhibits potent anti-cancer activities. CMTs is a potential suitable model for studies in human breast cancer research. In the present study, we separated DHA-untreated cells from CMTs cells to be a control group, the rest of the CMTs cells treated by DHA which were composed of three concentrations 5,10 as well as 20 µM. After that we cultivate the cells severally under the condition of 24, 48 and 72 h at 37 °C. CMTs cells were evaluated by Cell viability assay, Wound healing assay, Invasion assay and RT-PCR analysis for the expression of Slug, ZEB1, ZEB2 and Twist. Our results showed that DHA increased the inhibitory rate of CMTs cell and restrain TGF-ß1-induced migration and invasion of cells in a time and concentration reliant manner efficaciously. Our result also show DHA inhibits the expression of Slug, ZEB1, ZEB2 and Twist at the mRNA in vitro, the media concentration DHA (10 µM) decreased the expression level of the Slug, ZEB1, ZEB2 mRNA significantly. In conclusion, DHA inhibits canine mammary tumours cells migration and invasiveness by regulating the expression of EMT-related genes.

Long non-coding RNA ZEB1-AS1 promotes cell invasion and epithelial to mesenchymal transition through inducing ZEB1 expression in cervical cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer initiation and development. The purpose of the present study was to determine the functions and mechanisms of lncRNA ZEB1-AS1 in human cervical cancer (CC). METHODS: A total of 106 pairs of CC tissues and adjacent normal epithelial tissues were collected from CC patients who underwent resection. Three human CC cell lines (HeLa, C33A and SiHa) and a normal cervical cell line Crl-2614 and were transfected with human ZEB1-AS1 cDNA, or empty vector as the control. Then, cells were transfected with ZEB1-AS1-specific small interfering RNA (si-ZEB1-AS1), ZEB1-specific siRNA (si-ZEB1) or negative siRNA control (si-NC). The transfection efficiency was confirmed by RT-qPCR analysis. qPCR was applied to determine the qualification of RNA. Cell proliferation was investigated by MTT assay. The apoptosis rate of cells was detected by flow cytometer. Cell invasion was detected by transwell assay. Western blot was applied to determine the expression of proteins. CC xenografts in 12 male BALB/c athymic nude mice were established. And the tumor volumes were measured by vernier caliper. RESULTS: We found that ZEB1-AS1 expression was remarkably increased in human CC tissue samples and cell lines, and its expression levels were closely associated with poor prognosis of CC patients. Moreover, we found that knockdown of ZEB1-AS1 inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of CC cells in vitro and suppressed CC xenograft tumor growth in vivo. Mechanistically, we found that knockdown of ZEB1-AS1 significantly inhibited ZEB1 expression, and knockdown of ZEB1 could rescue the effects of ZEB1-AS1 overexpression in CC cells. CONCLUSION: In conclusion, our findings indicated that ZEB1-AS1 serves an oncogenic role in CC, which might become a potential prognostic indicator and therapeutic target in CC.

Forkhead box protein C1 promotes cell proliferation and invasion in human cervical cancer.

Increasing evidence has demonstrated that aberrant forkhead box protein C1 (FOXC1) expression contributes to tumorigenesis in multiple types of malignant tumor. However, the clinical significance and biological roles of FOXC1 in cervical cancer remain unknown. The expression levels of FOXC1 were examined in human cervical cancer tissues and cells using reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and western blotting. Furthermore, high FOXC1 expression was significantly associated with advanced clinical stages, a high degree of malignancy and a poor outcome. FOXC1 silencing inhibited cell growth and enhanced cell apoptosis. Knockdown of FOXC1 markedly suppressed cell migration and invasion in vitro, and resulted in downregulation of phosphorylated­RAC­α serine/threonine­protein kinase, proto­oncogene c­Myc and B­cell lymphoma 2. In conclusion, these data indicated that upregulation of FOXC1 contributed to the development of cervical cancer by increasing the growth and motility of the cervical cancer cells, thereby worsening the disease progression in these patients.

Serum BDNF concentration after delivery is associated with development of postpartum depression: A 3-month follow up study.

BACKGROUND: Our aim was to determine whether there is a relationship between serum brain-derived neurotrophic factor (BDNF) and postpartum depression (PPD) in a cohort Chinese population. METHODS: From May 1, 2014, to September 30, 2014, all eligible women not on medication for depression giving birth at the Fourth Affiliated Hospital of Harbin Medical University were consecutively recruited and followed up for 3 months. At 3 months postpartum, women were screened for depression using the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measure was an EPDS score of > or =12. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of BDNF at admission. Multivariate analyses were performed using logistic regression models. RESULTS: During the study period, 340 women were enrolled and completed follow-up. In those women, 37 women (10.9%) were considered as meeting criteria for PPD. Serum BDNF levels in women without PPD were significantly higher than those in women with PPD (P<0.0001). Based on the ROC curve, the optimal cutoff value of serum BDNF levels as an indicator for screening of PPD was estimated to be 12.0ng/ml, which yielded a sensitivity of 82.8% and a specificity of 72.6%, with the area under the curve at 0.809 (95%CI, 0.731-0.887). In multivariate analysis, there was an increased risk of PPD associated with BDNF levels ≤12.0ng/ml (OR 7.243, 95% CI: 3.883-12.746; P<0.0001) after adjusting for possible confounders. CONCLUSION: The present study demonstrates a strong relationship between reduced serum BDNF levels at admission and the development of PPD within the 3 months.

miR-181b functions as an oncomiR in colorectal cancer by targeting PDCD4.

Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.