C-type lectin 2D (CLEC2D) is upregulated in clear cell renal cell carcinoma (ccRCC) tissues and predicts poor prognosis.

Clear cell renal cell carcinoma (ccRCC) is known as the most common type of renal cancer. Recently, a series of advances have been made in targeted therapy for ccRCC. To combat this highly metastatic tumor, novel therapeutic targets still need to be developed. C-type lectins (CLECs) contain a characteristic C-type lectin-like domain and affect several physiological functions. The effects of C-type lectin 2D (CLEC2D) on cancer progression have been revealed in several types of cancers; however, its expression in ccRCC tissues, and the possible effects on the progression and metastasis of ccRCC, are still unclear. Herein, we found the high mRNA and protein levels of CLEC2D in ccRCC tissues. We further found that CLEC2D expression was correlated with the prognosis of ccRCC patients and correlated with the tumor size (p = 0.019*) of patients. In addition, CLEC2D affected tumor immune infiltration, confirmed by the further analysis. CLEC2D knockdown suppressed the proliferation of ccRCC cells in vitro and restrained ccRCC tumor growth and immune infiltration in mice. Therefore, we believe that CLEC2D has the potential to serve as a promising ccRCC therapeutic target.

[Retracted] KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the tumour images in Fig. 3A and the immunohistochemistry data in Fig. 3C on p. 7, and colony formation assay data shown in Fig. 4F on p. 8 were strikingly similar to data that had already appeared in previous publications. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 99, 2021; DOI: 10.3892/ijmm.2021.4932].

Deciphering Cell-Cell Interactions with Integrative Single-Cell Secretion Profiling.

Cell-cell interactions are the fundamental behaviors to regulate cellular activities. A comprehensive evaluation of intercellular interactions requires direct profiling of various signaling behaviors simultaneously at the single-cell level, which remains lacking. Herein, an integrative single-cell secretion analysis platform is presented to profile different secreted factors (four proteins, three extracellular vesicles (EV) phenotypes), spatial distances, and migration information (distances and direction) simultaneously from high-throughput paired single cells using an antibody-barcode microchip. Applying the platform to analyze the tumor-stromal and tumor-immune interactions with the human oral squamous cell carcinoma (OSCC) cell lines and primary OSCC cells reveals that the initial distances between cells would determine their migratory distances and direction to approach stable organization. The cell-cell in close proximity enhances protein secretions while attenuating EV secretions. Migration has a more profound correlation with protein secretions than EV secretions, in which absolute migration distance affects protein secretions significantly but not the direction. These findings highlight the significance of spatial organization in regulating cell signaling behaviors and demonstrate that the integrative single-cell secretion profiling platform is well-suited for a comprehensive dissection of intercellular communication and interactions, providing new avenues for understanding cell-cell interaction biology and how different signaling behaviors coordinate within the tumor microenvironment.

Knockdown of circ_CLIP2 regulates the proliferation, metastasis and apoptosis of glioma cells through miR-641/EPHA3/STAT3 axis.

A great amount of reaches have confirmed that circular RNAs (circRNAs) are novel regulators in glioma progression. Here, our work aimed to probe the specific role of circ_CLIP2 in glioma. The mRNA and protein expressions were analyzed by qRT-PCR and western blot, respectively. Cell viability, migration, invasion and apoptosis were examined by MTT assay, tranwell and flow cytometry assays, respectively. Moreover, the binding relationships between circ_CLIP2, microRNA (miR)-641 and erythropoietin-producing human hepatocellular (Eph)A3 were verified by dual luciferase reporter gene assay and/or RIP assay. The following data showed that circ_CLIP2 and EPHA3 were markedly increased in glioma tissues and cells, while miR-647 was downregulated. Gain- and loss-of-function experiments discovered that circ_CLIP2 knockdown remarkably inhibited cell proliferation, migration and invasion and promoted cell apoptosis of glioma cells, while these effects of circ_CLIP2 knockdown were abolished by miR-641 inhibition. Circ_CLIP2 was proved as a sponge of miR-641 to competitively upregulate EPHA3 expression. In addition, EPHA3 overexpression could abolish the inhibitory effects of miR-641 overexpression on the malignant behaviors of glioma cells by activating the signal transducer and activator of transcription 3 (STAT3). These findings elucidated that circ_CLIP2 knockdown suppressed glioma development by regulation of the miR-641/EP HA3/STAT3 axis, which provided a novel mechanism for understanding the pathogenesis of glioma.

Integration of Handheld Ultrasound or Automated Breast Ultrasound among Women with Negative Mammographic Screening Findings: A Multi-center Population-based Study in China.

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.

Compression Elastography and Shear Wave Ultrasound Elastography for Measurement of Brain Elasticity in Full-Term and Premature Neonates: A Prospective Study.

OBJECTIVES: To investigate the brain tissue elasticity in normal term and premature neonates using compression elastography and shear wave elastography. METHODS: This prospective observational study enrolled term and premature neonates admitted to the Third Affiliated Hospital of Guangzhou Medical University between July 2019 and December 2020. RESULTS: A total of 106 neonates, including 65 premature neonates and 41 term neonates, were enrolled. The elastic modulus of the frontal white matter in males was significantly lower than in females (11.67 ± 0.98 versus 12.25 ± 1.31, P = .030), but the shear wave velocity of the thalamus in males was significantly lower than in females (1.18 ± 0.13 versus 1.82 ± 0.10, P < .001). There was no significant correlation between real-time body weight and brain tissue elasticity including elastic modulus and shear wave velocity. But, the shear wave velocity of parietal white matter (r = 0.319, P = .014) and thalamus (r = -0.268, P = .040) and the elastic modulus of parietal white matter (r = 0.356, P = .006) were correlated with corrected gestational age. CONCLUSIONS: Clinicians may consider using elastography to determine brain tissue elasticity in term and preterm neonates.

Mapping secretome-mediated interaction between paired neuron-macrophage single cells.

Neuron-immune interaction through secreted factors contributes significantly to the complex microenvironment in the central nervous system that could alter cell functionalities and fates in both physiological and pathological conditions, which remains poorly characterized at the single-cell level. Herein, using a spatially patterned antibody barcode microchip, we realized the mapping of 12 different secretomes, covering cytokines, neurotrophic factors (NFs), and neuron-derived exosomes (NDEs) from high-throughput, paired single cells (≥ 600) simultaneously under normal conditions and an Alzheimer's disease (AD) model induced with amyloid beta protein 1-42 (Aß1-42). We applied the platform to analyze the secretion profiles from paired neuron-macrophage and neuron-microglia single cells with human cell lines. We found that pairwise neuron-macrophage interaction would trigger immune responses and attenuate neuron cells' secretion, while neuron-microglia interaction generally results in opposite outcomes in secretion. When neuron cells are induced with Aß1-42 protein into the AD model, both neuron-macrophage and neuron-microglia interactions lead to increased cytokines and NDEs and decreased NFs. Further analysis of AD patients' serum showed that NDEs were significantly higher in patients' samples than in the control group, validating our observation from the interaction assay. Furthermore, we resolved previously undifferentiated heterogeneity underlying the secretions from single-neuron cells. We found that the NDE and NF secretion was less dependent on the paracrine signaling between one another and that secretions from neuron cells would attenuate after differentiation with Aß1-42. This study demonstrates the mapping of the different secretomes from paired neuron-immune single cells, providing avenues for understanding how neurons and immune cells interact through the complex secretome network.

Lamin B2 contributes to the proliferation of bladder cancer cells via activating the expression of cell division cycle­associated protein 3.

Bladder cancer is the most common malignant tumor of the urinary system, and in China it is first among urogenital system tumors. More therapeutic targets are still urgently required to combat this disease. Lamin B2 (LMNB2) is a type of nuclear lamina filament protein, which is involved in multiple cellular processes, and known as an oncogene affecting the progression of multiple types of cancers. Although the multiple effects of LMNB2 on cancer progression have been elucidated, its possible role in bladder cancer remains unclear. In the present study, it was determined that LMNB2 expression was upregulated in human bladder cancer tissues, and its expression was correlated with the prognosis and the clinical features, including tumor stage (P=0.001) and recurrence (P=0.006) of patients with bladder cancer. In addition, it was further revealed that LMNB2 depletion inhibited bladder cancer cell proliferation, stimulated cell cycle arrest and apoptosis in vitro, and suppressed tumor growth of bladder cancer cells in mice. Furthermore, the present data revealed that LMNB2 promoted the proliferation of bladder cancer cells via transcriptional activation of CDCA3 expression. Therefore, the role of LMNB2 in bladder cancer progression was demonstrated, and may serve as a promising therapeutic target for bladder cancer treatment.

Spatial barcoding-enabled highly multiplexed immunoassay with digital microfluidics.

Digital microfluidics (DMF), facilitating independent manipulation of microliter samples, provides an ideal platform for immunoassay detection; however, suffering limited multiplexity. To address the need, herein we described a digital microfluidics (DMF) platform that realizes spatial barcoding on the Teflon-coated indium tin oxide (ITO) glass side to fulfill highly multiplexed immunoassay (10+) with low-volume samples (∼4 µL) in parallel, representing the highest multiplexing recorded to date for DMF-actuated immunoassay. Planar-based spatial immobilization of multiple capture antibodies was realized on a Teflon-coated ITO glass side, which was then used as the top plate of the DMF device. Droplets containing analytes, secondary antibodies, and fluorescent signaling reporters with low volume, which were electrically manipulated by our DMF control system, were shuttled sequentially along the working electrodes to complete the immuno-reaction. Evaluation of platform performance with recombinant proteins showed excellent sensitivity and reproducibility. To test the feasibility of our platform in analyzing multiplex biomarkers of the immune response, we used lipopolysaccharide-stimulated macrophages as a model system for protein secretion dynamics studies. As a result, temporal profiling of pro-inflammatory cytokine secretion dynamics was obtained. The spatial barcoding strategy presented here is easy-to-operate to enable a more comprehensive evaluation of protein abundance from biological samples, paving the way for new opportunities to realize multiplexity-associated applications with the DMF platform.

ARPC1A is regulated by STAT3 to inhibit ferroptosis and promote prostate cancer progression.

The aim of this study was to investigate the biological function and molecular mechanism of ARPC1A (actin related protein 2/3 complex subunit 1A) in prostate cancer progression. RT-qPCR and IHC results showed that the level of ARPC1A in prostate cancer tissues was significantly higher than that in adjacent tissues. The results of TCGA (the cancer genome atlas) database analysis showed that high expression of ARPC1A indicates poor prognosis in prostate cancer patients. In vitro functional experiments confirmed that downregulation of ARPC1A expression resulted in decreased cell viability and invasive ability of prostate cancer cells, as ARPC1A knockdown promoted ferroptosis. The transcriptional regulation mechanism of STAT3 (signal transduction and activators of transcription 3) on ARPC1A was elucidated by Co-IP, ChIP and luciferase reporter assays. In vivo experiments also supported the in vitro results. We propose that reduced ARPC1A expression inhibits prostate cancer cell viability and invasion in a ferroptotic manner. The ARPC1A level may serve as an independent predictor of prognosis in prostate cancer patients.

NCAPG Promotes the Proliferation of Renal Clear Cell Carcinoma via Mediating with CDK1.

Objective: Currently, lots of scholars have proved that the expression of NCAPG is associated with the prognosis of several cancers, while the relationship between NCAPG and renal clear cell carcinoma remains unclear, so the main aim of this research is to explore the effects of NCAPG on the progression of renal clear cell carcinoma. Methods: We observed the differential expression of NCAPG in several cancers from GEPIA online database, and the expression of NCAPG in renal clear cell carcinoma and normal tissue was compared and further verified by IHC assay. CCK-8 assay and clone formation experiment were conducted to observe the change of NCAPG on the proliferation. GraphPad was used for data analysis, and t-test and χ 2 analysis were used to analyze the correlation between NCAPG/CDK1 and renal clear cell carcinoma. Results: NCAPG was upregulated in renal clear cell carcinoma compared with the normal tissue, and the expression of NCAPG was associated with the clinical prognosis of pancreatic cancer especially with tumor size (P = 0.010). Knockdown NCAPG could restrain the proliferation of renal clear cell carcinoma. CDK1 was found to be tightly related with NCAPG, and the expression of CDK1 was also associated with the prognosis. Conclusions: NCAPG was upregulated in renal clear cell carcinoma, which was related with tumor size and overall survival. NCAPG might promote the proliferation of renal clear cell carcinoma via mediating CDK1. NCAPG/CDK1 complex might provide a new treatment strategy for lots of patients with renal clear cell carcinoma.

The Correlation of HK2 Gene Expression with the Occurrence, Immune Cell Infiltration, and Prognosis of Renal Cell Carcinoma.

Objectives: Hexokinase 2 (HK2) is one of the key factors involved in the development of several human cancers. However, its role in immune cell infiltration (ICI) and tumor development in renal cell carcinoma is not yet known. Thus, we aimed to explore its relationship with ICI, overall survival, and prognosis of renal cell carcinoma. Methods: In this study, RNA-seq data from renal cancer and normal tissues were extracted from TCGA and the relationship between HK2 expression and pathological features of RCC patients was analyzed using the GEPIA and UALCAN databases. Subsequently, Western blot and qRT-PCR were performed to analyze the protein and mRNA expression of HK2 in renal cell carcinoma tissues and cell lines. Lastly, various bioinformatics tools were applied to determine the immune cell infiltration, survival, and developing prediction model. Results: The analysis of RNA-seq data revealed a high expression of HK2 in renal cell carcinoma; furthermore, Western blot and qRT-PCR also showed high expression of HK2 in renal cancer tissues and cell lines. The high expression of HK2 showed a significant positive correlation with the advanced stage of the tumor, lymph node metastasis, and worst survival in renal carcinoma patients. The high expression of HK2 was further identified as an independent risk factor of RCC patients; it also showed a significant positive immune cell infiltration RCC tumor microenvironment including macrophages, B cells, neutrophils, dendritic cells, and CD8+ T cells. Conclusion: the expression of HK2 is positively correlated with the immune cell infiltration and prognosis of renal cell carcinoma patients, thus playing an important role in renal cancer development.

Angiogenesis and Functional Vessel Formation Induced by Interstitial Flow and Vascular Endothelial Growth Factor Using a Microfluidic Chip.

Angiogenesis occurs during both physiological and pathological processes. In this study, a microfluidic chip for the development of angiogenesis was utilized to assess angiogenic sprouting and functional vessel formation. We also found that vascular endothelial growth factor (VEGF) was a determinant of the initiation of vascular sprouts, while the direction of these sprouts was greatly influenced by interstitial flow. Isoforms of VEGF such as VEGF121, VEGF165, and VEGF189 displayed different angiogenic properties on the chip as assessed by sprout length and number, vessel perfusion, and connectivity. VEGF165 had the highest capacity to induce vascular sprouting among the three isoforms assessed and furthermore, also induced functional vessel formation. This chip could be used to analyze the effect of different angiogenic factors and drugs, as well as to explore the mechanism of angiogenesis induced by such factors.

Serum exosomal lncRNA XIST is a potential non-invasive biomarker to diagnose recurrence of triple-negative breast cancer.

Exosomal lncRNAs secreted by cancer cells can serve as potential biomarkers in the diagnosis and prognosis of various tumours. Here, we are committed to explore the diagnostic and prognostic value of serum exosomal XIST secreted by tumour cells to predict recurrence in patients with triple-negative breast cancer (TNBC). Significant increments in XIST and exo-XIST from tumour tissues and blood serum were found in reoccurring TNBC patients by comparison with non-recurrences. Levels of serum exo-XIST were only significantly increased in TNBC recurrence and no association with other clinicopathological parameters. Additionally, serum exo-XIST levels could be served as an assessment of change in the load of triple-negative breast cancer. Expressions of exo-XIST were markedly decreased after resection of the primary breast tumours and obviously elevated at the time of recurrence. Finally, an obvious association was identified between serum exo-XIST levels and a poorer overall survival (OS) in TNBC patients. Levels of serum exo-XIST may serve as a diagnostic and prognostic biomarker to predict the recurrent TNBC-loading status.

KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.

Bladder cancer (BC) is among the most common urinary system tumors with a high morbidity and mortality worldwide. Despite advancements being made in the diagnosis and treatment of bladder cancer, targeted therapy remains the most promising treatment, and novel therapeutic targets are urgently required in to improve the outcomes of patients with BC. Kinesin family member 4A (KIF4A) is a plus­end directed motor protein involved in the regulation of multiple cellular processes, such as mitosis and axon growth. Notably, KIF4A plays important roles in tumor growth and progression, and its expression is associated with the prognosis of several types of cancer. However, the potential role and molecular mechanisms of KIF4A in bladder cancer development remain unclear. The present study demonstrated that KIF4A was highly expressed in human BC tissues, and its expression was associated with patient clinicopathological characteristics, such as tumor stage (P=0.012) and with the prognosis of patients with BC. It was further found that KIF4A promoted the cell proliferation of bladder cancer both in vitro and in vivo. On the whole, the data presented herein provide evidence that KIF4A promotes the development of BC through the transcriptional activation of the expression of CDCA3. The present study indicates the involvement of KIF4A in the progression of BC and suggests that KIF4A may be a promising therapeutic target for the treatment of BC.

Circ_0057553/miR-515-5p Regulates Prostate Cancer Cell Proliferation, Apoptosis, Migration, Invasion and Aerobic Glycolysis by Targeting YES1.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant cancer in males worldwide. Circular RNAs (CircRNAs) are novel type of non-coding RNAs. Recently, circRNAs have been reported participating in various cancers, including prostate cancer. However, the function and mechanism of circ_0057553 remain to be elucidated. METHODS AND MATERIALS: The RNA expression levels of circ_0057553, miR-515-5p, YES proto-oncogene 1 (YES1) and glycolytic genes mRNA were detected by qRT-PCR in PCa tissues or cells. Western blotting was performed to analyze YES1 protein level. Cell viability, migration and invasion and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry. In addition, the effects of cell glycolysis were evaluated by measuring lactate production, glucose consumption and adenosine triphosphate (ATP) level. Moreover, dual-luciferase reporter assay was used to detect the target sites of circ_0057553 and miR-515-5p, miR-515-5p and YES1. RNA immunoprecipitation (RIP) was conducted to evaluate the target relationship between circ_0057553 and miR-515-5p. Xenograft mouse model was conducted to measure tumor formation in vivo. RESULTS: Circ_0057553 was significantly up-regulated in PCa tissues and cells. Knockdown of circ_0057553 inhibited cell viability, migration, invasion and glycolysis and facilitated apoptosis in PCa cells. Furthermore, circ_0057553 bound to miR-515-5p and miR-515-5p directly targeted YES1. Interestingly, miR-515-5p inhibitor partially rescued the function of circ_0057553 knockdown, while YES1 restored the effects of miR-515-5p overexpression. Circ_0057553 down-regulation remarkably decreased tumor volume and weight in vivo. CONCLUSION: Circ_0057553 affected PCa cell viability, migration, invasion, apoptosis and glycolysis through miR-515-5p/YES1 axis.

Ribosome Binding Protein 1 Correlates with Prognosis and Cell Proliferation in Bladder Cancer.

INTRODUCTION: Ribosome binding protein 1 (RRBP1) is reported to be correlated with tumor formation and progression. However, the role of RRBP1 in bladder cancer is unclear. In this study, we aimed to investigate the expression of RRBP1 and its influence on cell proliferation in bladder cancer. METHODS: Quantification real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to detect the expression levels of RRBP1 in 138 bladder cancer and matched adjacent normal bladder tissues. Then, the clinical significance of RRBP1 in bladder cancer was evaluated. The effect of RRBP1 on cell proliferation and its potential mechanism were further explored. RESULTS: Results show that the mRNA levels of RRBP1 in bladder cancer were significantly higher compared with those in normal tissues (P< 0.001). IHC results show the high-expression rate of RRBP1 in bladder cancer was 68.8%, which was significantly greater than those in normal tissues (40.6%, P< 0.001). RRBP1 high-expression was significantly associated with differentiation, T stage and lymph node metastasis in bladder cancer (P< 0.05). The overall survival time of patients with RRBP1 high-expression was significantly reduced compared to those with RRBP1 low-expression. Moreover, RRBP1 overexpression significantly promoted cell proliferation, which was correlated with Smad1/Smad3/TGF-ß1 signal pathway. CONCLUSION: RRBP1 high-expression correlates with prognosis and promotes cell proliferation in bladder cancer, which could be a potential biomarker.

MiR-1297 negatively regulates metabolic reprogramming in glioblastoma via repressing KPNA2.

Cancer cell growth is characterized by reprogrammed glucose metabolism and subsequent high rate of glycolysis. The metabolic reprogramming is essential for cell proliferation and drug resistance of cancer cells including glioblastoma (GBM). MicroRNAs play pivotal roles during GBM development. In the present study, we discovered a significant downregulation of miR-1297 in GBM. Decreased miR-1297 expression was associated with prolonged overall survival of patients with glioma. Overexpression of miR-1297 promoted cell proliferation and glycolysis in GBM cells. Bioinformatic analysis (TargetScan and miRanda) indicated that miR-1297 might target 3'UTR of KPNA2, a key regulator of glycolysis in GBM. The regulation was confirmed in a dual-luciferase reporter assay in GBM cells. Furthermore, overexpression of KPNA2 could reverse miR-1297 mimic induced cell growth arrest and inhibition of glycolysis in GBM cells. Finally, a negative correlation between miR-1297 and KPNA2 mRNA levels was observed in GBM tissues. Collectively, the data demonstrated that the abnormal metabolic reprogramming was driven by miR-1297 in GBM and suggested miR-1297 as a tumor suppressor.

CircPCNXL2 sponges miR-153 to promote the proliferation and invasion of renal cancer cells through upregulating ZEB2.

Increasing evidence showed that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and underlying mechanisms of circRNAs in clear cell renal cell carcinoma (ccRCC) remain unclear. In the present study, we identified a novel circRNA circPCNXL2, which was significantly upregulated in ccRCC by circular RNA microarray. Further analysis revealed that circPCNXL2 was significantly increased and correlated with poor overall survival of ccRCC patients. Function assays revealed that circPCNXL2 knockdown reduced RCC cells proliferation, invasion in vitro, and decreased tumor growth in vivo. In mechanism study, we showed that circPCNXL2 could be bind to miR-153 as a miRNA sponge to regulate ZEB2 expression in RCC progression. In addition, our data reported that the effects of circPCNXL2 inhibition on RCC cells proliferation and invasion could be abolished by miR-153 inhibitors. Altogether, we demonstrated that circPCNXL2 could regulate RCC cells proliferation and invasion by miR-153/ZEB2 axis, suggesting circPCNXL2 might serve as a potential therapeutic target for ccRCC treatment.

High lncRNA HULC expression is associated with poor prognosis and promotes tumor progression by regulating epithelial-mesenchymal transition in prostate cancer.

INTRODUCTION: Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs) play critical roles in tumor progression and development. However, the expression pattern and biological function of lncRNA HULC (highly upregulated in liver cancer) in prostate cancer (PCa) remain largely unclear. MATERIAL AND METHODS: The expression of lncRNA HULC in 53 paired PCa tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The χ2 test was used to explore the association of lncRNA HULC expression with clinicopathologic features. Kaplan-Meier analysis was used to detect the association between HULC expression and overall survival of PCa patients. Furthermore, the function of HULC in cell growth and metastasis was detected in PCa cells. RESULTS: Our data showed that HULC expression was upregulated in PCa tissues and cell lines compared to adjacent non-tumor tissues and the normal prostate cell line RWPE-1 (p < 0.05). High HULC expression was positively associated with advanced clinicopathologic features and poor overall survival (OS) for PCa patients (p < 0.05). HULC inhibition suppressed PCa cell growth and metastasis both in vitro and in vivo (p < 0.05). Furthermore, HULC knockdown reduced N-cadherin and vimentin expression and increased E-cadherin expression in PCa cells (p < 0.05). CONCLUSIONS: Our data suggested that lncRNA HULC might play oncogenic roles in PCa progression, which provided a novel therapeutic strategy for PCa patients.