METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner.

BACKGROUND: The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. The aim of this study was to investigate the expression, roles, and mechanisms of action of the RNA methyltransferase methyltransferase-like protein 16 (METTL16) in HCC. METHODS: The expression of METTL16 and RAB11B-AS1 was determined by RT-qPCR. The regulation of RAB11B-AS1 by METTL16 was investigated by RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and RNA stability assays. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of METTL16 and RAB11B-AS1. RESULTS: METTL16 was upregulated in HCC, and its increased expression was correlated with poor prognosis of HCC patients. METTL16 promoted HCC cellular proliferation, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumoral growth in vivo. METTL16 directly bound long noncoding RNA (lncRNA) RAB11B-AS1, induced m6A modification of RAB11B-AS1, and decreased the stability of RAB11B-AS1 transcript, leading to the downregulation of RAB11B-AS1. Conversely to METTL16, RAB11B-AS1 is downregulated in HCC, and its decreased expression was correlated with poor prognosis of patients with HCC. Furthermore, the expression of RAB11B-AS1 was negatively correlated with METTL16 in HCC tissues. RAB11B-AS1 repressed HCC cellular proliferation, migration, and invasion, promoted HCC cellular apoptosis, and inhibited HCC tumoral growth in vivo. Functional rescue assays revealed that overexpression of RAB11B-AS1 reversed the oncogenic roles of METTL16 in HCC. CONCLUSIONS: This study identified the METTL16/RAB11B-AS1 regulatory axis in HCC, which represented novel targets for HCC prognosis and treatment.

Identification of the tumor­suppressive role of circular RNA­FOXO3 in colorectal cancer via regulation of miR­543/LATS1 axis.

Colorectal cancer (CRC) is a common malignancy with significant prevalence and mortality rates. Circular RNA FOXO3 (circ­FOXO3; hsa_circ_0006404) has been reported to be involved in cancer regulation; however, its role in CRC is yet to be fully elucidated. Therefore, the aim of the present study was to investigate the effect of circ­FOXO3 on CRC progression and identify its underlying mechanism. In the present study, the expression of circ­FOXO3 was investigated in CRC tissues and cells via reverse transcription­quantitative PCR. A Cell Counting Kit­8 and colony formation assays were used to assess cell proliferation. The cell migratory and invasive abilities were detected using the Transwell migration and invasion assays. The luciferase assay and RNA pull­down assay were conducted to verify the relationship of circ­FOXO3, microRNA (miR)­543 and Large tumor suppressor kinase 1 (LATS1). The results demonstrated that circ­FOXO3 expression was downregulated in CRC tissues and cells, and was associated with poor overall survival of patients with CRC. Moreover, circ­FOXO3 was associated with tumor size, distant metastasis, differentiation, lymph node metastasis and TMN stages of patients with CRC. circ­FOXO3 overexpression suppressed CRC cell proliferation, migration and invasion. Luciferase assay and RNA pull­down assay results indicated that circ­FOXO3 functioned as a sponge for miR­543. In addition, circ­FOXO3 increased the expression of LATS1 via sponging miR­543, thus inhibiting CRC cell aggressive features. Collectively, the present results suggested that circ­FOXO3 inhibited CRC metastasis and progression via elevated LATS1 expression by sponging miR­543. Therefore, circ­FOXO3 may be a promising target for CRC therapy.

Long non­coding RNA CASC19 promotes glioma progression by modulating the miR­454­3p/RAB5A axis and is associated with unfavorable MRI features.

Glioma is one of the most common malignancies of the nervous system. Long non­coding RNAs (lncRNAs) are regulators involved in the progression of tumors. The present study aimed to determine the role of lncRNA cancer susceptibility 19 (CASC19) in glioma and its underlying molecular mechanism. Reverse transcription­quantitative PCR was performed to detect CASC19 and microRNA (miR)­454­3p expression in glioma and normal brain tissues. Ras­related protein in brain 5A (RAB5A) expression in glioma cells was also analyzed via western blotting. The relationship between CASC19 expression, clinicopathological parameters and MRI characteristics in patients with glioma was analyzed. Cell Counting Kit­8, BrdU, wound healing and Transwell assays were adopted to detect glioma cell proliferation, migration and invasion, respectively. The dual­luciferase reporter gene and RNA immunoprecipitation experiments were conducted to verify the targeting relationship between CASC19 and miR­454­3p, and between miR­454­3p and RAB5A. The results revealed that CASC19 expression was significantly upregulated in glioma tissues and cell lines. CASC19 expression was also positively associated with tumor diameter and pathological grade. Additionally, its high expression was closely associated with tumor MRI signal heterogeneity and peritumoral edema. CASC19 upregulation promoted glioma cell proliferation and metastasis, while CASC19­knockdown demonstrated the opposite effect. CASC19 sponged miR­454­3p, which indirectly increased RAB5A expression. The results demonstrated that the CASC19/miR­454­3p/RAB5A axis is involved in the promotion of glioma progression.

A Novel Prediction Tool Based on Multiparametric Magnetic Resonance Imaging to Determine the Biopsy Strategy for Clinically Significant Prostate Cancer in Patients with PSA Levels Less than 50 ng/ml.

PURPOSE: To develop and internally validate nomograms to help choose the optimal biopsy strategy among no biopsy, targeted biopsy (TB) only, or TB plus systematic biopsy (SB). PATIENTS AND METHODS: This retrospective study included a total of 385 patients who underwent magnetic resonance imaging (MRI)-guided TB and/or SB at our institute after undergoing multiparametric MRI (mpMRI) between 2015 and 2018. We developed models to predict clinically significant prostate cancer (csPCa) based on suspicious lesions from a TB result and based on the whole prostate gland from the results of TB plus SB or SB only. Nomograms were generated using logistic regression and evaluated using receiver-operating characteristic (ROC) curve analysis, calibration curves and decision analysis. The results were validated using ROC curve and calibration on 177 patients from 2018 to 2019 at the same institute. RESULTS: In the multivariate analyses, prostate-specific antigen level, prostate volume, and the Prostate Imaging Reporting and Data System score were predictors of csPCa in both nomograms. Age was also included in the model for suspicious lesions, while obesity was included in the model for the whole gland. The area under the curve (AUC) in the ROC analyses of the prediction models was 0.755 for suspicious lesions and 0.887 for the whole gland. Both models performed well in the calibration and decision analyses. In the validation cohort, the ROC curve described the AUCs of 0.723 and 0.917 for the nomogram of suspicious lesions and nomogram of the whole gland, respectively. Also, the calibration curve detected low error rates for both models. CONCLUSION: Nomograms with excellent discriminative ability were developed and validated. These nomograms can be used to select the optimal biopsy strategy for individual patients in the future.

Initial experience with a novel method for cognitive transperineal magnetic resonance imaging-targeted prostate biopsy.

A cognitive magnetic resonance imaging (MRI)-targeted prostate biopsy conducted by an experienced clinician enhances the detection rate of (high-grade) prostate cancer; however, this method is less successful in the hands of inexperienced surgeons. Therefore, an alternative method of conducting a cognitive MRI-targeted biopsy that can be successfully performed by the inexperienced clinicians should be developed. Ninety-six males suspected of prostate cancer were analyzed using systematic biopsy and cognitive MRI-targeted biopsy based on our novel three-dimensional matrix positioning method. Typically, the core principle of the latter procedure was to put the MRI and ultrasound images into the same virtual coordinate system. Afterward, the targeted biopsy was transformed to target a coordinate for the suspected lesion in the MRI. Subsequently, patients were assessed for the presence/absence of prostate cancer or high-grade prostate cancer. According to our results, the overall detection rate of prostate cancer was 70.8% (68/96), and the detection rate of high-grade prostate cancer was 56.3% (54/96). Specifically, the detection rate of prostate cancer by systematic biopsy was 54.2% (52/96) and that by targeted biopsy was 59.4% (57/96; P = 0.560). Clearly, the combined application of targeted biopsy could remarkably increase the detection rates of prostate cancer (P = 0.025) and high-grade prostate cancer (P = 0.009). Taken together, the findings of this study suggest that the combination of systematic biopsy with our three-dimensional matrix positioning-driven cognitive-targeted biopsy is superior to systematic biopsy in detecting prostate cancer and high-grade prostate cancer.

Xanthones from the herb of Swertia elata and their anti-TMV activity.

Two new xanthones (1-2), together with four known ones (3-6), were isolated from whole herb of Swertia elata. Their structures were elucidated by spectroscopic methods including extensive 1D- and 2D-NMR techniques. Their anti-tobacco mosaic virus (anti-TMV) activity test revealed that 1-6 showed weak anti-TMV activities with inhibition rate in the range of 15.2-28.8% at the concentration of 20 µM.

Removal of numerous vesical magnetic beads with a self-made magnetic sheath.

INTRODUCTION: Sexual curiosity and the quest for sexual excitement are the most frequent reasons for patients to introduce foreign bodies into the urethra or the bladder. Imagination and surgical skill are essential for urologists to retrieve such vesical foreign bodies. AIM: The aim of this study was to describe a novel method for retrieving vesical magnetic beads, which were inserted for autoeroticism by a male adolescent, with a self-made "magnetic sheath." METHODS: A 21-year-old young man inserted more than one hundred small magnetic beads into his urethra for sexual excitement, which lately caused symptoms of gross hematuria, frequent urination, and acute lower abdominal pain when walking or urinating. We invented a magnetic sheath by fixing a magnetic bead on the tip of an F9.5 ureteral access sheath to remove the foreign bodies in a minimally invasive way. MAIN OUTCOME MEASURE: The feasibility of using magnetic sheath to remove vesical foreign bodies; and operation duration. RESULTS: Under direct visualization of an F8/9.8 ureteroscope, the magnetic sheath could firmly attach to the magnetic bead inside the bladder and could easily pull out 5 to 15 beads each time. It took about 5 minutes to remove all of the 125 magnetic beads by utilizing our magnetic sheath. CONCLUSIONS: The self-made magnetic sheath can make the task of removal of magnetic foreign bodies easy to urologists, requiring less time and surgical skills. The new equipment provides a new method for urologists to deal with the challenging task of removing metal vesical foreign bodies which were self-inserted for masturbation.

[Preliminary report of Nd: YAG laser embolysis for branch retinal artery occlusion].

OBJECTIVE: In this study, the clinical effect of the Nd: YAG laser embolysis on branch retinal artery occlusion was evaluated. METHODS: A fundus contact lens was used to focus the Nd: YAG laser on the embolus within the retinal arteriole. 0.8 to 0.9 mJ of laser pulse was delivered directly to the embolus. Fundus photographs were taken before and immediately after the treatment. Follow-up time ranged from 2 weeks to 4 months, average about 7 weeks. Seven cases received the treatment, including 5 male and 2 female patients. Age of those cases ranged from 49 to 73, average 61 years. The duration of the disease ranged from 1 to 60 days, average 13 days. RESULTS: Before treatment, visual acuity ranged from 0.06 to 0.8. Embolus can be detected in all the 7 cases. After treatment, all the cases showed immediate recovery of blood flow in the occluded arteriole both in fundus examination and fundus fluorescein angiography. The vision in the patients was improved in the follow-up. Visual acuity ranged from 0.2 approximately 1.0. In most cases, visual field defect still existed in the ischemic area. Complications included local retinal hemorrhages in some cases and vitreous hemorrhage, but those hemorrhages were gradually absorbed and did not affect the final visual prognosis. CONCLUSIONS: Nd: YAG laser embolysis for branch retinal artery occlusion is an effective treatment and the treatment is relatively safe.