Progressive Pulmonary Fibrosis Is Caused by Elevated Mechanical Tension on Alveolar Stem Cells.

Fibrosis can develop in most organs and causes organ failure. The most common type of lung fibrosis is known as idiopathic pulmonary fibrosis, in which fibrosis starts at the lung periphery and then progresses toward the lung center, eventually causing respiratory failure. Little is known about the mechanisms underlying the pathogenesis and periphery-to-center progression of the disease. Here we discovered that loss of Cdc42 function in alveolar stem cells (AT2 cells) causes periphery-to-center progressive lung fibrosis. We further show that Cdc42-null AT2 cells in both post-pneumonectomy and untreated aged mice cannot regenerate new alveoli, resulting in sustained exposure of AT2 cells to elevated mechanical tension. We demonstrate that elevated mechanical tension activates a TGF-ß signaling loop in AT2 cells, which drives the periphery-to-center progression of lung fibrosis. Our study establishes a direct mechanistic link between impaired alveolar regeneration, mechanical tension, and progressive lung fibrosis.

RPL35A drives ovarian cancer progression by promoting the binding of YY1 to CTCF promoter.

Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.

Stem cells in pulmonary alveolar regeneration.

The lungs are constantly exposed to the external environment and are therefore vulnerable to insults that can cause infection and injury. Maintaining the integrity and barrier function of the lung epithelium requires complex interactions of multiple cell lineages. Elucidating the cellular players and their regulation mechanisms provides fundamental information to deepen understanding about the responses and contributions of lung stem cells. This Review focuses on advances in our understanding of mammalian alveolar epithelial stem cell subpopulations and discusses insights about the regeneration-specific cell status of alveolar epithelial stem cells. We also consider how these advances can inform our understanding of post-injury lung repair processes and lung diseases.

Podocyte-specific deletion of ubiquitin carboxyl-terminal hydrolase L1 causes podocyte injury by inducing endoplasmic reticulum stress.

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a unique component of the ubiquitin-proteasome system (UPS), which has multiple activities in maintaining intracellular ubiquitin levels. We previously reported the aberrant low expression of UCHL1 in podocytes of non-immune complex-mediated glomerulonephritis, and recent studies indicate that anti-UCHL1 antibody was responsible for the refractory minimal change disease (MCD), but the specific effect of UCHL1 to the podocytopathy has not been determined. Therefore, we generated podocyte-specific UCHL1 gene knockout (UCHL1cre/cre) rats model. Podocyte-specific UCHL1 knockout rats exhibited severe kidney damage, including segmental/global glomerulosclerosis, kidney function damage and severe proteinuria, compared with littermate control. Subsequently, by carrying out mass spectrometry analysis of isolated glomeruli of rats, abnormal protein accumulation of ECM-receptor Interaction was found in UCHL1cre/cre rats. Mechanistic studies in vivo and in vitro revealed that aberrant protein accumulation after UCHL1 deficiency induced endoplasmic reticulum (ER) stress, unfolded protein reaction (UPR) to reduce the protein level of podocyte skeleton proteins, and CHOP mediated apoptosis as well, which related to the dysfunction of the ubiquitin-proteasome system with decreased free monomeric ubiquitin level, thereby affecting protein ubiquitination and degradation. In addition, inhibition of ER stress by 4-PBA could attenuate the degree of ER stress and podocyte dysfunction. Our study indicates that UCHL1 is a potential target for preventing podocytes injury in some non-immune complex-mediated glomerulopathy.

Research on the Vision-Based Dairy Cow Ear Tag Recognition Method.

With the increase in the scale of breeding at modern pastures, the management of dairy cows has become much more challenging, and individual recognition is the key to the implementation of precision farming. Based on the need for low-cost and accurate herd management and for non-stressful and non-invasive individual recognition, we propose a vision-based automatic recognition method for dairy cow ear tags. Firstly, for the detection of cow ear tags, the lightweight Small-YOLOV5s is proposed, and then a differentiable binarization network (DBNet) combined with a convolutional recurrent neural network (CRNN) is used to achieve the recognition of the numbers on ear tags. The experimental results demonstrated notable improvements: Compared to those of YOLOV5s, Small-YOLOV5s enhanced recall by 1.5%, increased the mean average precision by 0.9%, reduced the number of model parameters by 5,447,802, and enhanced the average prediction speed for a single image by 0.5 ms. The final accuracy of the ear tag number recognition was an impressive 92.1%. Moreover, this study introduces two standardized experimental datasets specifically designed for the ear tag detection and recognition of dairy cows. These datasets will be made freely available to researchers in the global dairy cattle community with the intention of fostering intelligent advancements in the breeding industry.

Secondary ocular hypertension due to tentorial dural arteriovenous fistula: a case report.

BACKGROUND: Tentorial dural arteriovenous fistulas (TDAVFs) are abnormal shunts between meningeal arteries and the intradural venous system located in the tentorial dura mater, which typically manifest with haemorrhage or progressive neurological disorders. TDAVFs with pure ocular presentation have been rarely reported. CASE PRESENTATIONS: The case of a 56-year-old man presented with unilateral eye redness, proptosis and elevated intraocular pressure was reported herein, which was caused by a TDAVF. The fistula was fed by the left posterior cerebral artery and posterior meningeal artery. The drainage was into the basal vein and internal cerebral veins, which led the arterial blood flow forward to the left superior ophthalmic vein directly. The redundant blood flow caused the rise of episcleral venous pressure, leading to the clinical presentations. Gamma knife radiosurgery was performed then considering the delicate vascular structure and its deep location. The corkscrew hyperaemia was gradually alleviated after the surgery, but the intraocular pressure remained elevated at follow-ups. CONCLUSION: Dural arteriovenous fistulas which are not directly connected to cavernous sinus could cause ocular presentations like proptosis, eye redness and ocular hypertension.

Unilateral pigmented paravenous retinochoroidal atrophy with acute angle-closure glaucoma: a case report.

BACKGROUND: Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon fundus disease characterized by perivenous aggregations of pigment clumps and retinochoroidal atrophy distributed along the retinal veins. We report a Chinese female case of unilateral PPRCA with acute angle-closure glaucoma (AACG). CASE PRESENTATION: A 50-year-old Chinese female presented with vision loss and elevated intraocular pressure (IOP) in the right eye and then underwent trabeculectomy. She referred to our clinic for further evaluation and treatment. The funduscopic examination revealed grayish retinochoroidal atrophy and osteocyte-like pigment clumping lesions along the retinal veins and peripapillary preretinal hemorrhage in the right eye. The patient also presented with AACG in the same eye on the basis of past medical history of acute attack, shallow anterior chamber depth (ACD), narrow angle showed by ultrasound biomicroscopy (UBM) and glaucomatous neuropathy identified by optical coherence tomography (OCT). Other examinations like fluorescein fundus angiography (FFA), electroretinogram (ERG) and electrooculography (EOG) all confirmed the aforementioned diagnose. CONCLUSION: PPRCA is a rare disease, uncommon in females and symmetrical in both eyes. We present a rare case of unilateral PPRCA accompanied with AACG.

Proximal Tubular Lats2 Ablation Exacerbates Ischemia/Reperfusion Injury (IRI)-Induced Renal Maladaptive Repair through the Upregulation of P53.

The Hippo pathway mediates renal maladaptive repair after acute kidney injury (AKI), which has been considered a driving force in the progression to chronic kidney disease (CKD). LATS2, a core kinase of the Hippo pathway, exerts non-Hippo-dependent functions in the regulation of the cell cycle and cell fate, providing new insights into AKI and further repair. However, its role remains unknown. Here, we utilized a proximal tubular Lats2 conditional knockout mouse strain (Lats2-CKO) to evaluate the effect of LATS2 deficiency on ischemia/reperfusion-induced AKI-to-CKD transition. Lats2-CKO mice presented with more severe tubular maladaptive repair, inflammatory infiltration, interstitial fibrosis, and apoptosis following AKI. Importantly, we discovered that Lats2 ablation caused the activation of p53, with increased levels of cellular apoptotic molecules (p21, Bax, and cleaved caspase-3), and decreased levels of anti-apoptotic molecules (Bcl-2 and Bcl-xL). Pifithirin-α (p53 inhibitor) effectively attenuated renal fibrosis, inflammation, and apoptosis in Lats2-CKO mice after AKI. Consistently, in vitro Lats2 overexpression decreased p53, p21, Bax and cleaved caspase 3 expression after hypoxia/reoxygenation (H/R) treatment. Of note, the phosphorylation of MDM2, which promotes the ubiquitination degradation of p53, at site Ser186 was decreased in Lats2-CKO kidneys, but increased by Lats2 overexpression in vitro. Therefore, LATS2 deficiency aggravated ischemia/reperfusion injury (IRI)-induced maladaptive repair via regulating the tubular MDM2-p53 axis in AKI-to-CKD transition.

Blocking ribosomal protein S6 phosphorylation inhibits podocyte hypertrophy and focal segmental glomerulosclerosis.

Ribosomal protein S6 (rpS6) phosphorylation mediates the hypertrophic growth of kidney proximal tubule cells. However, the role of rpS6 phosphorylation in podocyte hypertrophy and podocyte loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS) remains undefined. Here, we examined rpS6 phosphorylation levels in kidney biopsy specimens from patients with FSGS and in podocytes from mouse kidneys with Adriamycin-induced FSGS. Using genetic and pharmacologic approaches in the mouse model of FSGS, we investigated the role of rpS6 phosphorylation in podocyte hypertrophy and loss during development and progression of FSGS. Phosphorylated rpS6 was found to be markedly increased in the podocytes of patients with FSGS and Adriamycin-induced FSGS mice. Genetic deletion of the Tuberous sclerosis 1 gene in kidney glomerular podocytes activated mammalian target of rapamycin complex 1 signaling to rpS6 phosphorylation, resulting in podocyte hypertrophy and pathologic features similar to those of patients with FSGS including podocyte loss, leading to segmental glomerulosclerosis. Since protein phosphatase 1 is known to negatively regulate rpS6 phosphorylation, treatment with an inhibitor increased phospho-rpS6 levels, promoted podocyte hypertrophy and exacerbated formation of FSGS lesions. Importantly, blocking rpS6 phosphorylation (either by generating congenic rpS6 knock-in mice expressing non-phosphorylatable rpS6 or by inhibiting ribosomal protein S6 kinase 1-mediated rpS6 phosphorylation with an inhibitor) significantly blunted podocyte hypertrophy, inhibited podocyte loss, and attenuated formation of FSGS lesions. Thus, our study provides genetic and pharmacologic evidence indicating that specifically targeting rpS6 phosphorylation can attenuate the development of FSGS lesions by inhibiting podocyte hypertrophy and associated podocyte depletion.

Dihydroartemisinin improves hypercholesterolemia in ovariectomized mice via enhancing vectorial transport of cholesterol and bile acids from blood to bile.

The increase of concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum of postmenopausal women is the important risk factor of the high morbidity of cardiovascular diseases of old women worldwide. To test the anti-hypercholesterolemia function of dihydroartemisinin (DHA) in postmenopausal women, ovariectomized (OVX) mice were generated, and DHA were administrated to OVX mice for 4 weeks. The blood and liver tissues were collected for biochemical and histological tests respectively. The mRNA and protein expression levels of genes related to metabolism and transport of cholesterol, bile acid and fatty acid in the liver or ileum were checked through qPCR and western blot. DHA could significantly reduce the high concentrations of TC and LDL-C in the serum and the lipid accumulation in the liver of ovariectomized mice. The expression of ABCG5/8 was reduced in liver of OVX mice, and DHA could up-regulate the expression of them. Genes of transport proteins for bile salt transport from blood to bile, including Slc10a1, Slco1b2 and Abcb11, were also significantly up-regulated by DHA. DHA also down-regulated the expression of Slc10a2 in the ileum of OVX mice to reduce the absorption of bile salts. Genes required for fatty acid synthesis and uptake, such as Fasn and CD36, were reduced in the liver of OVX mice, and DHA administration could significantly up-regulate the expression of them. These results demonstrated that DHA could improve hypercholesterolemia in OVX mice through enhancing the vectorial transport of cholesterol and bile acid from blood to bile.

Multidrug-Resistant Acinetobacter baumannii May Cause Patients to Develop Polymicrobial Bloodstream Infection.

Background: The incidence of polymicrobial bloodstream infections is increasing, the clinical characteristics of polymicrobial Acinetobacter baumannii bloodstream infections (AB-BSI) are unclear, and there are no reports of polymicrobial AB-BSI in mainland China. Therefore, our objective was to identify the clinical characteristics, risk factors, and outcomes of polymicrobial AB-BSI versus monomicrobial AB-BSI. Methods: A retrospective survey of all patients with AB-BSI from January 1, 2015, to December 31, 2019, and their clinical data were collected and analyzed by reviewing electronic medical records. All data were compared and analyzed between groups of monomicrobial and polymicrobial AB-BSI. Risk factors for polymicrobial AB-BSI were assessed using multivariable logistic regression analysis. Results: A total of 204 patients were included, of which 39 (19.1%) were patients with polymicrobial AB-BSI. The main sources of the pathogenicity of polymicrobial Acinetobacter baumannii bloodstream infections were skin and soft tissue (38.5% vs. 16.4%, p=0.002). Resistance to piperacillin/tazobactam as an independent factor for polymicrobial AB-BSI was found in multivariate analysis. Patients with polymicrobial AB-BSI had longer hospital stays compared to those with monomicrobial AB-BSI. However, there was no significant difference in mortality between the two groups. Conclusions: Polymicrobial AB-BSI accounted for a significant proportion among all AB-BSI, and it did not influence mortality but was related to slightly longer total hospital stays. Multidrug resistance was associated with the development of polymicrobial AB-BSI but does not directly lead to polymicrobial AB-BSI, whereas resistance to piperacillin/tazobactam was highly correlated with polymicrobial AB-BSI. Therefore, while treating A. baumannii bloodstream infections, clinicians cannot ignore the multidrug-resistant A. baumannii, especially piperacillin/tazobactam-resistant A. baumannii, which may predispose to the development of polymicrobial AB-BSI.

Tailoring Bond Microenvironments and Reaction Pathways of Single-Atom Catalysts for Efficient Water Electrolysis.

Single-atom sites (SASs) are commonly stabilized and influenced by neighboring atoms in the host; disclosing the structure-reactivity relationships of SASs in water electrolysis is one of the grand challenges originating from the tremendous wealth of support materials with complex structures. Through a multidisciplinary view of the design principles, synthesis strategies, characterization techniques, and theoretical analysis of structure-performance correlations, this timely Review is dedicated to summarizing the most recent progress in tailoring bond microenvironments on different supports and discussing the reaction pathways and performance advantages of different SAS structures for water electrolysis. The essence and mechanisms of how SAS structures influence electrocatalysis and the critical requirements for future developments are discussed. Finally, the challenges and perspectives are also provided to stimulate the practical, widespread utilization of SAS catalysts in water-splitting electrolyzers.

Nuclear exclusion of YAP exacerbates podocyte apoptosis and disease progression in Adriamycin-induced focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease with poor clinical outcomes. Podocyte loss via apoptosis is one important mechanism underlying the pathogenesis of FSGS. Recently, Yes-associated-protein (YAP), a key downstream protein in the Hippo pathway, was identified as an activator for multiple gene transcriptional factors in the nucleus to control cell proliferation and apoptosis. To investigate the potential role of YAP in the progression of FSGS, we examined kidney samples from patients with minimal change disease or FSGS and found that increases in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in human FSGS. Utilizing an established mT/mG transgenic mouse model and primary cultured podocytes, we found that YAP was distributed uniformly in nucleus and cytoplasm in the podocytes of control animals. Adriamycin treatment induced gradual nuclear exclusion of YAP with enhanced phospho-YAP/YAP ratio, accompanied by the induction of podocyte apoptosis both in vivo and in vitro. Moreover, we used verteporfin to treat an Adriamycin-induced FSGS mouse model, and found YAP inhibition by verteporfin induced nuclear exclusion of YAP, thus increasing podocyte apoptosis and accelerating disease progression. Therefore, our findings suggest that YAP nuclear distribution and activation in podocytes is an important endogenous anti-apoptotic mechanism during the progression of FSGS.

Berberine improves liver injury induced glucose and lipid metabolic disorders via alleviating ER stress of hepatocytes and modulating gut microbiota in mice.

Liver injury mediated by endoplasmic reticulum (ER) stress can cause many kinds of liver diseases including hepatic glucose and lipid metabolic disorders, and long term liver injury would lead to cirrhosis and hepatic cancer. Therefore, effective drugs for treating liver injury are urgent in need. Berberine is a multifunctional drug of traditional Chinese medicine, and it can improve various liver diseases. To study the effects of berberine on ER stress-induced liver injury, tunicamycin was administrated to C57BL/6 mice with or without berberine pre-treatment. H&E staining was used to check the morphology and histology of liver tissues. The serum and liver tissues were harvested to test biochemical indexes and the expression levels of genes related with glucose and lipid metabolism, ER stress and unfold protein response (UPR). 16S rDNA sequence technology was conducted to check the fecal microbiota. Pre-administration with berberine could alleviate the excess accumulation of triglyceride (TG) in the liver of mice treated with tunicamycin. Tunicamycin administration caused significant increase of the expression level of genes related to ER stress and UPR, such as CHOP, Grp78 and ATF6, but the berberine pre-treatment could significantly downregulate the expression level of these genes. Tunicamycin administration resulted in increased ratio of Prevotellaceae to Erysipelotrichaceae at the family level of the fecal microbiota in mice, and this trend was reversed by the pre-treatment of berberine. These results demonstrated that berberine could improve liver injury induced hepatic metabolic disorders through relieving ER stress in hepatocytes and regulating gut microbiota in mice.

Intelligent target recognition for distributed acoustic sensors by using both manual and deep features.

Effective information mining of fiber-optic distributed acoustic sensors (DAS) is so important that it attracts more and more public attention, and various manual and deep feature extraction methods have been developed. However, either way it has limits; for example, the manual features contain insufficient information, and the deep features could be unreliable because of the overfitting problem. Thus, in this paper, to avoid the disadvantages of each and make full use of the effective information carried by DAS signals, an intelligent target recognition method by utilizing both manual and deep features is proposed. The manual features are first extracted in the time domain, frequency domain, semantic domain, and from dynamic models, which are fused with the deep features extracted by a four-layer 1D convolutional neural network (CNN) through feature engineering. The features are ranked and then selected by a combined weighting method of analysis of variance and maximum information coefficient. Then finally, an optimal classifier is selected by comparing support vector machine, extreme gradient boost, random forest, and native Bayesian. In the test with real field data, four types of features, which include the manual features, the CNN features, and the combined features without and with selection, are compared with these different classifiers. As a result, it shows the combined features without selection can improve the identification ability of DAS compared with the recognition with only manual or deep features. The combined features with selection can further improve the computation efficiency and save up to 90% of time with a performance degradation of less than 1%.

AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype.

BACKGROUND: Kidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 (APOL1) variants that are more common in those of African descent. METHODS: To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury-associated genes. We also collected peripheral blood for APOL1 genotyping. RESULTS: This case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis. CONCLUSIONS: Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a "two-hit" combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity's resemblance with HIV-associated nephropathy, we propose the term COVID-19-associated nephropathy to describe it.

Plakoglobin is involved in cytoskeletal rearrangement of podocytes under the regulation of UCH-L1.

UCH-L1 is a de-ubiquitination enzyme comprehensively distributed in neural cells and podocytes, which is involved in several kinds of nervous system and kidney related diseases. Our previous studies have demonstrated the aberrant up-regulation of UCH-L1 in podocytes of renal diseases, but how dose podocytes are injured by up-regulated UCH-L1 is waiting to be elucidated. Here, we observed the cytoskeleton rearrangement in podocytes with over-expression of UCH-L1, accompanied with a down-regulation of synaptopodin and RhoA, which are closely related to cytoskeletal stabilization. However, we did not see any alteration of RhoA ubiquitination level under the stimulation of UCH-L1 in podocytes. Subsequently, mass spectrum was applied in UCH-L1-flag immunoprecipitation and plakoglobin was screened out, which was among the UCH-L1-combined proteins and most likely related to cytoskeleton rearrangement. Our experiment demonstrates UCH-L1 may not injure podocytes cytoskeleton through a direct regulation on RhoA/Synaptopodin, but through the regulation of plakoglobin, which could be a promising target for treatment of renal disease in the future.

Activation of Wnt/ß-catenin pathway causes insulin resistance and increases lipogenesis in HepG2 cells via regulation of endoplasmic reticulum stress.

BACKGROUND: Wnt/ß-catenin signaling is involved in glucose and lipid metabolism, but the mechanism is not clear yet. AIM: The objective is to study mechanisms of Wnt/ß-catenin signaling on regulating hepatocytes metabolism. METHODS: Real-time qPCR, Western blot, and Oil-red O staining methods were used. RESULTS: The Wnt/ß-catenin signaling was activated in hepatocytes by CP21R7, and the level of phosphorylated IRS-1 (Ser307) and TRB3 were significantly increased, while the levels of phosphorylated IRS-1 (Tyr612) and phosphorylated Akt were decreased. Moreover, the expression of FGF21, FAS, SCD1, PPARγ and ADRP was significantly increased. The expression of ATF4, ATF5, eIF2α, GRP78, CHOP and phosphorylated level of PERK were also increased. The expression of FGF21 and TRB3 was significantly down-regulated, and the lipid droplets were notably reduced after the ER stress was inhibited by TUDCA. The expression of FGF21 was significantly decreased when the IRE1 pathway of the UPR was inhibited by STF-083010. CONCLUSIONS: Activation of Wnt/ß-catenin signaling pathway could cause insulin resistance and lipogenesis in hepatocytes via regulation of the IRE1 pathway of the ER stress and UPR, providing new targets for the treatment of metabolic disorders.

Knockdown of lncRNA PVT1 inhibits prostate cancer progression in vitro and in vivo by the suppression of KIF23 through stimulating miR-15a-5p.

BACKGROUND: Prostate cancer (PCa) greatly threatens men's lives, with high incidence and mortality. Recently, the research of long non-coding RNAs (lncRNAs) has made breakthroughs in the development of human cancers. This study aimed to figure out the role and action mechanism of lncRNA PVT1 (PVT1) in PCa. METHODS: The expression of PVT1, microRNA-15a-5p (miR-15a-5p) and kinesin family member 23 (KIF23) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assays, respectively. The protein levels of KIF23 and proliferation, apoptosis, and epithelial-mesenchymal transition (EMT)-related markers were quantified by western blot. The relationship between miR-15a-5p and PVT1 or KIF23 was predicted by starBase v2.0 and verified by dual-luciferase reporter assay. Xenograft assay was conducted to determine the role of PVT1 in vivo. RESULTS: The expression of PVT1 and KIF23 was enhanced, while miR-15a-5p expression was reduced in PCa tissues and cells. PVT1 interference inhibited proliferation, migration and invasion but promoted apoptosis of PCa cells. MiR-15a-5p was a target of PVT1, and KIF23 was a target of miR-15a-5p. The inhibition of miR-15a-5p reversed the effects of PVT1 interference and suppressed the roles of KIF23 knockdown. KIF23 expression was regulated by PVT1 through miR-15a-5p. PVT1 interference blocked PCa progression in vivo. CONCLUSION: PVT1 knockdown had effects on the progression of PCa by inhibiting the expression of KIF23 via enriching miR-15a-5p in vitro and in vivo, suggesting that PVT1 might be a novel biomarker for the treatment of PCa.