LncRNA MAFG-AS1 deregulated in breast cancer affects autophagy and progression of breast cancer by interacting with miR-3612 and FKBP4 invitro.

PURPOSE: We aimed to explore the function and competing endogenous RNA (ceRNA) pathway of MAFG-AS1 in breast cancer. METHODS: qRT-PCR assay identified the expression of MAFG-AS1, miR-3612 and FKBP4. We used Western blot analysis to test the autophagy related protein levels in breast cancer cells. Functional assays such as Cell Counting Kit-8 (CCK8) assay, BrdU proliferation assay, Caspase-3 activity detection were used to identify the function of MAFG-AS1, miR-3612 and FKBP4 in breast cancer cells. Mechanism assays were used to verify the interacting relationship among MAFG-AS1, miR-3612 and FKBP4, including RNA pull down assay, RNA immunoprecipitation (RIP) assay and luciferase reporter assay. RESULTS: MAFG-AS1 and FKBP4 were both up-regulated in breast cancer tissues. MAFG-AS1 could function as an oncogene in breast cancer to activate cell proliferation, and inhibit cell apoptosis and autophagy. Meanwhile, MAFG-AS1 could sponge miR-3612 to elevate the expression of FKBP4. Besides, FKBP4 could activate the cell proliferation and inhibit cell apoptosis and autophagy, which could relieve the inhibitory effect of miR-3612 on breast cancer cells. CONCLUSION: MAFG-AS1 could activate breast cancer progression via modulating miR-3612/FKBP4 axis in vitro.

Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10.

MicroRNAs (miRNAs/miRs) are important biomarkers for the progression of intervertebral disc degeneration (IDD). We investigated the role of miR-30d in IDD progression through its interactions with forkhead box O3 (FOXO3) and C-X-C motif ligand 10 (CXCL10). We first measured the expression of miR-30d, FOXO3, and CXCL10 in NP cells cultured from IDD patients. RNA-immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were then employed to test the relationship among miR-30d, FOXO3, and CXCL10. Besides, gain- and loss-of function approaches were performed to assess the functional roles of miR-30d and FOXO3 in IDD in vitro and in vivo. We found high expression of miR-30d and CXCL10 and low expression of FOXO3 in IDD. We showed that miR-30d specifically targeted FOXO3, and that down-regulation of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by increasing the expression of FOXO3. Besides, FOXO3 inhibited apoptosis of NP cells by downregulation of CXCL10 expression. Moreover, inhibition of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by decreasing CXCL10. Furthermore, findings in the mouse IDD model confirmed the inhibitory role of decreased miR-30d in IDD progression. Thus, we show that downregulation of miR-30d could promote the proliferation of NP cells by increasing FOXO3 and decreasing CXCL10 expression, which may provide a novel therapeutic target for IDD.

MicroRNA-200c promotes osteogenic differentiation of human bone mesenchymal stem cells through activating the AKT/ß-Catenin signaling pathway via downregulating Myd88.

During the human bone formation, the event of osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) is vital, and recent evidence has emphasized the important role of microRNAs (miRNAs) in osteogenic differentiation of hBMSCs. This study aims to examine the potential effects of miR-200c in osteogenic differentiation of hBMSCs and understand their underlying mechanisms. HBMSCs were obtained via human bone marrow. During osteogenic induction and differentiation, cells were transfected with different plasmids with the intention of investigating the roles of miR-200c on osteogenic differentiation, calcium salt deposition, alkaline-phosphatase (ALP) activity, mineralized nodule formation, osteocalcin (OCN) content, and proliferation of osteoblasts. Following transfection, dual luciferase reporter gene assay was conducted so as to explore the correlation between miR-200c and Myd88. Moreover, the AKT/ß-Catenin signaling pathway was blocked with an AKT/ß-Catenin inhibitor, AKTi, to investigate its involvement. The hBMSCs were successfully isolated from human bone marrow. Myd88 was determined as a target gene of miR-200c. Gain and loss-of-function assays confirmed that overexpression of miR-200c, or silencing of Myd88 promoted osteogenic differentiation, increased calcium salt deposition, ALP activity, mineralized nodule formation, and enhanced the proliferation of osteoblasts following osteogenic differentiation of hBMSCs. Meanwhile, the downregulation of miR-200c has been shown to have the opposite effect. Furthermore, these findings showed that the miR-200c overexpression activated the AKT/ß-Catenin signaling pathway by targeting Myd88. To sum up, the miR-200c upregulation induces osteogenic differentiation of hBMSCs by activating the AKT/ß-Catenin signaling pathway via the inhibition of Myd88, providing a target for treatment of bone repair.

MicroRNA-377 exerts a potent suppressive role in osteosarcoma through the involvement of the histone acetyltransferase 1-mediated Wnt axis.

It has been demonstrated that microRNAs (miRNAs) may contribute to tumorigenesis and tumor growth in osteosarcoma (OS), which is a primary malignant tumor of bone frequently diagnosed in adolescents and young people. The purpose of our investigation was to evaluate the functional relevance of miR-377 in OS and to investigate whether the mechanism was related to the histone acetyltransferase 1 (HAT1)-mediated Wnt signaling pathway. By screening differentially expressed genes in microarray GSE47572, HAT1 was found to be a candidate gene of interest. Besides, the regulatory miRNA (miR-377) of HAT1 was also selected. The interaction among miR-377, HAT1, and the Wnt signaling pathway was evaluated. In addition, the miR-377 expression was altered in OS cells (U-2OS and SOSP-9607) to assess the in vitro cell apoptosis and the in vivo tumor growth. OS tissues presented elevated HAT1 expression and decreased miR-377 expression. A putative miR-377 binding site in HAT1 3'-UTR HAT1 was verified. Cells with miR-377 overexpression or HAT1 silencing were observed to exhibit reduced HAT1 expression and promoted apoptosis, accompanied by blockade of Wnt signaling. Moreover, the in vivo experiment revealed that miR-377 overexpression or HAT1 silencing inhibited tumor growth and reduced tumor size in nude mice. Taken together, our results conclude that miR-377 may promote OS cell apoptosis through inactivation of the HAT1-mediated Wnt signaling pathway, highlighting the potential therapeutic effect of miR-377 on OS treatment.

SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. One hundred and six MB samples were examined. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA, FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and α-synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA revealed the ability of this gene to inhibit tumor invasion and induce apoptosis. Methylation-specific PCR and pyrosequencing analysis showed that epigenetic mechanisms, rather than DNA hypermethylation, might play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.

Mir-449a, a potential diagnostic biomarker for WNT group of medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The 5 year disease-free survival rate is rather low. There is a consensus that MB can be divided into at least four clinically, transcriptionally, and genetically distinct molecular variants, being designated as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4. It poses a great challenge to the design of therapeutic strategy for MB patients. Intensive clinical intervention, including high dose radiotherapy, is commonly used in treatment of high risk MB, most of which are considered to be Group 3 patients. But such intensive therapy should be avoided to protect neurologic function of patients in the lower risk WNT group. In present study, MB subgroup assignment in formalin-fixed paraffin embedded (FFPE) specimens from 45 Chinese patients were performed by Nanostring platform using 22 well-known signature genes. Based on comparative expression profiles of miRNA real-time PCR microarray in MB cells with and without treatment of demethylation reagent, as well as MSP assay, miR-449a was demonstrated to be significantly silenced by aberrant DNA methylation in tumor cells. Real-time PCR showed that expression level of miR-449a in WNT group was significantly different from other subgroups, although it was down-regulated in most of the MB samples. In conclusion, current study demonstrates for the first time the feasibility of using the Nanostring assay for subgrouping of MBs in Chinese patients. In addition, MiR-449a, a candidate tumor suppressor regulated by hypermethylation, is a novel potential diagnostic marker for WNT group of MBs.

mtDNA release promotes cGAS-STING activation and accelerated aging of postmitotic muscle cells.

The mechanism regulating cellular senescence of postmitotic muscle cells is still unknown. cGAS-STING innate immune signaling was found to mediate cellular senescence in various types of cells, including postmitotic neuron cells, which however has not been explored in postmitotic muscle cells. Here by studying the myofibers from Zmpste24-/- progeria aged mice [an established mice model for Hutchinson-Gilford progeria syndrome (HGPS)], we observed senescence-associated phenotypes in Zmpste24-/- myofibers, which is coupled with increased oxidative damage to mitochondrial DNA (mtDNA) and secretion of senescence-associated secretory phenotype (SASP) factors. Also, Zmpste24-/- myofibers feature increased release of mtDNA from damaged mitochondria, mitophagy dysfunction, and activation of cGAS-STING. Meanwhile, increased mtDNA release in Zmpste24-/- myofibers appeared to be related with increased VDAC1 oligomerization. Further, the inhibition of VDAC1 oligomerization in Zmpste24-/- myofibers with VBIT4 reduced mtDNA release, cGAS-STING activation, and the expression of SASP factors. Our results reveal a novel mechanism of innate immune activation-associated cellular senescence in postmitotic muscle cells in aged muscle, which may help identify novel sets of diagnostic markers and therapeutic targets for progeria aging and aging-associated muscle diseases.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

BACKGROUND: "Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. METHODS: We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. RESULTS: All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. CONCLUSIONS: Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

Nuclear softening mediated by Sun2 suppression delays mechanical stress-induced cellular senescence.

Nuclear decoupling and softening are the main cellular mechanisms to resist mechanical stress-induced nuclear/DNA damage, however, its molecular mechanisms remain much unknown. Our recent study of Hutchinson-Gilford progeria syndrome (HGPS) disease revealed the role of nuclear membrane protein Sun2 in mediating nuclear damages and cellular senescence in progeria cells. However, the potential role of Sun2 in mechanical stress-induced nuclear damage and its correlation with nuclear decoupling and softening is still not clear. By applying cyclic mechanical stretch to mesenchymal stromal cells (MSCs) of WT and Zmpset24-/- mice (Z24-/-, a model for HGPS), we observed much increased nuclear damage in Z24-/- MSCs, which also featured elevated Sun2 expression, RhoA activation, F-actin polymerization and nuclear stiffness, indicating the compromised nuclear decoupling capacity. Suppression of Sun2 with siRNA effectively reduced nuclear/DNA damages caused by mechanical stretch, which was mediated by increased nuclear decoupling and softening, and consequently improved nuclear deformability. Our results reveal that Sun2 is greatly involved in mediating mechanical stress-induced nuclear damage by regulating nuclear mechanical properties, and Sun2 suppression can be a novel therapeutic target for treating progeria aging or aging-related diseases.

Balanced below- and above-ground growth improved yield and water productivity by cultivar renewal for winter wheat.

Breeding cultivars that can maintain high production and water productivity (WP) under various growing conditions would be important for mitigating freshwater shortage problems. Experiments were carried out to assess the changes in yield and WP of different cultivars by breeding and traits related to the changes using tubes with 1.05 m depth and 19.2 cm inner diameter buried in the field located in the North China Plain. Six winter wheat cultivars released from the 1970s to 2010s were assessed under three water levels for three seasons. The results indicated that yield was on average improved by 19.9% and WP by 21.5% under the three water levels for the three seasons for the cultivar released in the 2010s as compared with that released in the 1970s. The performance of the six cultivars was relatively stable across the experimental duration. The improvement in yield was mainly attributed to the maintenance of higher photosynthetic capacity during the reproductive growth stage and greater above-ground biomass accumulation. These improvements were larger under wet conditions than that under dry conditions, indicating that the yield potential was increased by cultivar renewal. Traits related to yield and WP improvements included the increased harvest index and reduced root: shoot ratio. New cultivars reduced the redundancy in root proliferation in the topsoil layer, which did not compromise the efficient utilization of soil moisture but reduced the metabolic input in root growth. Balanced above- and below-ground growth resulted in a significant improvement in root efficiency at grain yield level up to 40% from the cultivars released in the 1970s to those recently released. The results from this study indicated that the improved efficiency in both the above- and below-parts played important roles in enhancing crop production and resource use efficiency.

Enhancing anti-tumor efficacy and immune memory by combining 3p-GPC-3 siRNA treatment with PD-1 blockade in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with a high mortality rate and presents a major challenge for human health. Activation of multiple oncogenes has been reported to be strongly associated with the progression of HCC. Moreover, the immunosuppressive tumor microenvironment (TME) and the host immune system are also implicated in the development of malignant HCC tumors. Glypican-3 (GPC-3), a proteoglycan involved in the regulation of cell proliferation and apoptosis, is aberrantly expressed in HCC. We synthesized a short 5'-triphosphate (3p) RNA targeting GPC-3, 3p-GPC-3 siRNA, and found that it effectively inhibited subcutaneous HCC growth by raising type I IFN levels in tumor cells and serum and promoting tumor cell apoptosis. Moreover, 3p-GPC-3 siRNA was able to enhance the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells while reducing the proportion of regulatory T cells (Tregs) in the TME. Most intriguingly, a blocking anti-PD-1 antibody improved the anti-tumor effect of 3p-GPC-3 siRNA, predominantly by activating the immune response, reversing immune exhaustion, and improving immune memory. Our study suggests that the combination of 3p-GPC-3 siRNA administration and PD-1 blockade may represent a promising therapeutic strategy for HCC.

Multi-slice spiral computed tomography in differential diagnosis of gastric stromal tumors and benign gastric polyps, and gastric stromal tumor risk stratification assessment.

BACKGROUND: The biological characteristics of gastric stromal tumors are complex, and their incidence has increased in recent years. Gastric stromal tumors (GST) have potential malignant tendencies, and the probability of transformation into malignant tumors is as high as 20%-30%. AIM: To investigate the value of multi-slice spiral computed tomography (MSCT) in the differential diagnosis of GST and benign gastric polyps, and GST risk stratification assessment. METHODS: We included 64 patients with GST (GST group) and 60 with benign gastric polyps (control group), confirmed by pathological examination after surgery in PLA General Hospital, from January 2016 to June 2021. The differences in the MSCT imaging characteristic parameters and enhanced CT values between the two groups before surgery were compared. According to the National Institutes of Health's standard, GST is divided into low- and high-risk groups for MSCT imaging characteristic parameters and enhanced CT values. RESULTS: The incidences of extraluminal growth, blurred boundaries, and ulceration in the GST group were significantly higher than those in the control group (P < 0.05). The CT values and enhanced peak CT values in the arterial phase in the CST group were higher than those in the control group (P < 0.05). The MSCT differential diagnosis of GST and gastric polyp sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and areas under the curve (AUCs) were 73.44 %, 83.33%, 26.56%, 16.67%, 0.784, respectively. The receiver operating characteristic curves were plotted with the arterial CT value and enhanced peak CT value, with a statistical difference. The results showed that the sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and AUC value of arterial CT in the differential diagnosis of GST and gastric polyps were 80.18%, 62.20%, 19.82%, 37.80%, and 0.710, respectively. The sensitivity, specificity, misdiagnosis rate, missed diagnosis rate, and AUC value of the enhanced peak CT value in the differential diagnosis of GST and gastric polyps were 67.63%, 60.40%, 32.37%, 39.60%, and 0.710, respectively. The incidence of blurred lesion boundaries and ulceration in the high-risk group was significantly higher than that in the low-risk group (P < 0.05). The arterial phase and enhanced peak CT values in the high-risk group were significantly higher than those in the low-risk group (P < 0.05). CONCLUSION: Presurgical MSCT examination has important value in the differential diagnosis of GST and gastric benign polyps and can effectively evaluate the risk grade of GST patients.

Histone H3.3 G34-mutant Diffuse Gliomas in Adults.

The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P<0.001). Overall, 19 of the 30 patients were diagnosed of glioblastoma with the primitive neuronal component, and 8 were glioblastoma. The molecular profiling analysis revealed higher frequencies of Olig-2 loss of expression, TP53 mutation, ATRX mutation, PDGFRA mutation, and MGMT promoter methylation (P<0.05) in H3.3 G34-mutant gliomas than IDH/H3 wild-type gliomas. No TERT promoter mutation and only 1 case of EGFR amplification were detected in the H3.3 G34-mutant cohort, the frequencies of which were significantly higher in the IDH/H3 wild-type cohort. A dismal prognosis was observed in H3.3 G34-mutant patients comparing to IDH/H3 wild-type cohort (overall survival: 14 vs. 22 mo; P=0.026). Univariate and multivariate analyses showed that the extent of resection and TP53 mutation were independently affecting prognosis. The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.

Rapamycin inhibits the proliferation and apoptosis of gastric cancer cells by down regulating the expression of survivin.

BACKGROUND/AIMS: Gastric cancer is the second cause of cancer death worldwide. The prognosis of gastric cancer is poor due to its aggressiveness and resistance to chemotherapy. It has been reported that mTOR signaling pathway plays an important role in the development of several cancers. Rapamycin is an inhibitor of mTOR signaling pathway. This study aimed to observe the effects of rapamycin on the proliferation, apoptosis and invasiveness in human gastric cancer cell lines, SGC-7901 and MKN-45, and its mechanisms. METHODOLGY: Different concentrations of rapamycin (5 nM, 10 nM, 20 nM and 40 nM) were used in our research. MTT and flow cytometry assays were used to detect the proliferation and apoptosis of SGC-7901 and MKN-45 cells. Transwell assay was used to observe the invasive ability of gastric cancer cells. To observe the mRNA and protein expression of mTOR and survivin, RT-PCR and western blot assays were used. RESULTS: Our data showed that rapamycin could inhibit the proliferation and the invasive ability of SGC-7901 and MKN-45 cells. It also could induce the apoptosis of these two gastric cancer cell lines. These effects were observed in a dose dependent manner. The mRNA and protein expression of mTOR and survivin were inhibited by rapamycin as assessed by RT-PCR and western blot. CONCLUSIONS: Rapamycin could inhibit the proliferation and the invasive ability and induce the apoptosis of human gastric cancer cells in vitro. It might exert its biological effects through the inhibition of mTOR and survivin.

Correlation between rs13347 polymorphism of CD44 gene and the risk of occurring breast cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: With the attention paid to the heritability of breast cancer, the search for the genetic susceptibility gene of breast cancer has become a hot spot. At present, a number of studies have explored the relationship between rs13347 polymorphism of cluster of differentiation 44 (CD44) gene and breast cancer, but the research conclusions are inconsistent. Therefore, we will use this meta-analysis to explore the role of this gene polymorphism in breast cancer susceptibility. METHODS: The search time is set from the establishment of the database in March 2021 in this study. The search database include China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Journal Service Platform, and China Biology Medicine disc, PubMed, EMBASE, Web of Science and the Cochrane Library. The subjects are observational studies on the relationship between rs13347 polymorphism of CD44 gene and breast cancer (including case-control study, cross-sectional study and a cohort study). The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by two researchers independently. The data are statistically analyzed by Stata 16.0 software. RESULTS: Based on the existing studies, this study will systematically evaluate the relationship between CD44 gene rs13347 polymorphism and breast cancer. CONCLUSION: This study will provide evidence-based medical evidence to clarify the role of CD44 gene polymorphism in breast cancer, and provide help for the early detection and preventive intervention of breast cancer. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/WBC7F.

A Novel miR-98 Negatively Regulates the Resistance of Endometrial Cancer Cells to Paclitaxel by Suppressing ABCC10/MRP-7.

Endometrial cancer (EC) is one of the most frequent gynecological tumors, and chemoresistance is a major obstacle to improving the prognosis of EC patients. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have recently emerged as crucial chemoresistance regulators that alter the levels of downstream target genes. Multidrug Resistance Protein 7 (MRP-7/ABCC10) is an ATP-binding cassette transporter that causes the resistance to anti-cancer drugs. The purpose of this research is to determine whether MRP-7 has a role in mediating the sensitivity of EC cells to paclitaxel and whether the expression of MRP-7 is regulated by miR-98 and lncRNA NEAT1. We reported that the levels of MRP-7 were significantly increased in EC tissues and associated with an unfavorable prognosis. Downregulation of MRP-7 in EC cells sensitized these cells to paclitaxel and reduced cell invasion. PLAUR serves as a downstream molecule of MRP-7 and facilitates paclitaxel resistance and EC cell invasiveness. Moreover, miR-98 serves as a tumor suppressor to inhibit MRP-7 expression, leading to the repression of paclitaxel resistance. Furthermore, a novel lncRNA, NEAT1, was identified as a suppressor of miR-98, and NEAT1 could upregulate MRP-7 levels by reducing the expression of miR-98. Taken together, these findings demonstrate that upregulation of MRP-7 and NEAT1, and downregulation of miR-98 have important roles in conferring paclitaxel resistance to EC cells. The modulation of these molecules may help overcome the chemoresistance against paclitaxel in EC cells.

The effects of cages implantation on surgical and adjacent segmental intervertebral foramina.

OBJECTION: The overarching goal of our research was to compare the clinical and radiological outcomes with different sizes of cages implantation in anterior cervical discectomy and fusion (ACDF), and to evaluate the effects on surgical and adjacent segmental intervertebral foramina. METHODS: The clinical data of 61 patients were analyzed retrospectively. The radiological data included the surgical intervertebral disk space height before (H0) and after surgery (H), the preoperative mean height of adjacent segments (Hm), the area and height of the surgical and adjacent segment foramen, the surgical segmental Cobb angle (α1), and C2-7Cobb angle (α2). The calculation of clinical data was conducted by Japanese Orthopaedic Association Scores (JOA), the recovery rate of JOA scores and visual analog scales (VAS). In accordance with the different ranges of distraction (H/Hm), patients were classified into three groups: group A (H/Hm<1.20, n=13), group B (1.20≤H/Hm≤1.80, n=37), and group C (H/Hm>1.80, n=11). RESULTS: After the operation and at the final follow-up, our data has demonstrated that the area and height of surgical segmental foramen all increased by comparing those of preoperation in three groups (all P<0.05). However, except for a decrease in group C (all P<0.05), the adjacent segmental foramina showed no significant changes (all P>0.05). The area and height of the surgical segment foramen and the distraction degree were positively correlated (0

Long non-coding RNA (lncRNA) HOXB-AS3 promotes cell proliferation and inhibits apoptosis by regulating ADAM9 expression through targeting miR-498-5p in endometrial carcinoma.

OBJECTIVE: Long non-coding RNA (lncRNA) expression is closely related to the pathogenesis and progression of various tumors. In this study, we investigated the mechanisms of lncRNA HOXB cluster antisense RNA 3 (HOXB-AS3), miRNA(miR)-498-5p, and disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) in endometrial carcinoma (EC) cells. METHODS: The expression levels of lncRNA HOXB-AS3 in EC tissues and cells were detected using RT-qPCR assays. The effects of HOXB-AS3 knockdown on EC cell proliferation and apoptosis were measured using CCK-8 assays, colony formation assays, and flow cytometry. In addition, putative miR-498-5p binding sites were identified in HOXB-AS3 and ADAM9. The targeted relationships were further verified using dual-luciferase reporter and RNA pull-down assays. RESULTS: HOXB-AS3 expression was upregulated in EC tissues and cells. EC cell proliferation and viability decreased significantly in HOXB-AS3 knockdown groups. A putative miR-498-5p binding site in HOXB-AS3 was verified. Inhibition of miR-498-5p rescued the effects of HOXB-AS3 knockdown on cell proliferation and apoptosis. Finally, ADAM9 was verified as a direct target gene of miR-498-5p. CONCLUSIONS: Our results suggest that lncRNA HOXB-AS3 is highly expressed in EC tissues and cells. Downregulation of HOXB-AS3 inhibits cell proliferation and promotes apoptosis in EC cells. HOXB-AS3 can upregulate ADAM9 expression by sponging miR-498-5p.

Magnetic resonance imaging features of minimal-fat angiomyolipoma and causes of preoperative misdiagnosis.

BACKGROUND: Minimal-fat angiomyolipoma (mf-AML) is often misdiagnosed as renal cell carcinoma before surgery. AIM: To analyze the magnetic resonance imaging (MRI) features of mf-AML and the causes of misdiagnosis by MRI before operation. METHODS: A retrospective analysis was performed on ten patients with mf-AML confirmed by surgical pathology, all of whom underwent preoperative MRI examination to analyze the morphological characteristics and MRI signals of the tumor. RESULTS: MRI revealed a circular-like mass in 4/10 (40%) patients, an oval mass in 6/10 patients (60%), a mass with a capsule in 9/10 patients (90%), and a mass with a lipid component in 7/10 patients (70%). The diameter of the masses in all ten patients was from 11 to 47 mm; the diameter was between 11 mm and 40 mm in 8/10 (80%) patients and between 40 mm and 47 mm in 2/10 (20%) patients. CONCLUSION: An oval morphological characteristic is strong evidence for the diagnosis of mf-AML, while a capsule and lipids are atypical manifestations of mf-AML.