Expression and clinical significance of NLRC5 in hepatocellular carcinoma.

NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Molecular Detection and Characterization of Cryptosporidium spp. and Giardia duodenalis in Dairy Calves from Ningxia, China.

PURPOSE: Cryptosporidium spp. and Giardia duodenalis are two important foodborne human and animal parasites that can be disseminated through both food and water, leading to diarrheal disease. Nevertheless, available information on the circumstances of Cryptosporidium and Giardia duodenalis from Ningxia is limited. METHODS: A total of 208 stool samples of dairy calves derived from large-scale farms (> 1000 heads) of five cities randomly in Ningxia were gathered randomly, were amplified and analyzed by nested PCR based on the three target genes (18S rRNA, gp60 and tpi)and phylogenetic systematics. RESULTS: The prevalence of cryptosporidiosis and giardiasis in dairy calves in Ningxia were 13.0% (27/208 samples, 95% CI 9.1-18.2%) and 1.9% (4/208, 95% CI 0.8-4.9%) respectively. Three Cryptosporidium species appeared in this study which are Cryptosporidium parvum (C. parvum), Cryptosporidium andersoni (C. andersoni) and Cryptosporidium ryanae (C. ryanae) based on the 18S rRNA gene sequence. IIdA15G1 and IIdA13G1 belonging to the subtypes of Cryptosporidium were detected by the gp60 PCR. The genotypes of Giardia duodenalis were only assemblage E through the amplification of the triosephosphate-isomerase gene (tpi gene). CONCLUSION: There is a risk of transmission to humans in Ningxia because of zoonotic genotypes (C. parvum, C. andersoni, assemblage E) and subtypes (IId) of Cryptosporidium spp. and G. duodenalis in dairy calves, and it is necessary to pay attention to the disease to prevent a widespread epidemic of the disease with the purpose to protect human and livestock health.

The Superconductivity in Bi-Doped BaFe2As2 Single Crystals.

We have successfully synthesized a series of Bi-doped BaFe2As2 high-quality single crystals for the first time. X-ray diffraction (XRD) patterns show an expansion of lattice parameter c with Bi doping, indicating a negative pressure effect. By investigating the resistivity, a Fermi liquid (FL) to non-Fermi liquid (NFL) crossover is observed from normal state to antiferromagnetic order state, accompanied by three superconducting transitions labeled as SC I, SC II and SC III, which are supposed to be induced by three superconducting realms with various Bi concentrations. Thus, we propose that the NFL behavior is closely related to the presence of superconductivity. The magnetic susceptibility measurements further speculate that the SC I and SC III phases should exhibit filamentary superconductivity while the SC II exhibits a possible bulk superconductivity of TC~7 K.

Nonreciprocal coupling modulated difference-sideband generation in a double-cavity optomechanical system.

We theoretically study the difference-sideband generation in a double-cavity optomechanical system with nonreciprocal coupling. Beyond the conventional linearized description of optomechanical interactions, we derive analytical expressions for the efficiency of difference-sideband generation by using a perturbation method. Here we investigate bistable behaviors of the system and show the difference-sideband generation modulated by the nonreciprocal coupling strength between the two cavities. We find that the nonreciprocal coupling strength can not only affect the bistability of the system but also lead to different efficiencies of difference-sideband generation at low power. To achieve high efficiency of difference-sideband generation, we give the optimal matching conditions under different parameter mechanisms. Especially as the power increases, we find new matching conditions with remarkable difference-sideband generation emerging, which is attribute to the strong coherence between the cavity field and the mechanical oscillator. Furthermore, a feasible scheme to obtain difference-sideband generation by employing multiple adjustable variables is proposed. Our results may find applications in nonreciprocal optical frequency combs and communications, and provide a potential method for precision measurements and on-chip manipulation of light transmission.

Efficacy of TACE Combined with Lenvatinib Plus Sintilimab for Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava and/or Right Atrium.

Purpose: To validate the safety and effectiveness of transarterial chemoembolization (TACE) combination with lenvatinib and sintilimab in treating hepatocellular carcinoma (HCC) patients with inferior vena cava (IVC) and/or right atrium (RA) tumor thrombosis (TT). Methods: This study retrospectively analyzed HCC patients with IVC and/or RA TT treated with TACE combined with lenvatinib plus sintilimab. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the anti-tumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results: A total of 58 patients were screened for eligibility between March 2019 and May 2022. At the time of data collection, 48.2% of patients were still receiving treatment. The median follow-up was 23.5 months. The ORR was 48.3%, the DCR was 91.4%, the median OS was 17.3 months, and the median PFS was 13.0 months. The ORR for IVC/RA TT was 62.1%, DCR was 94.9%, and the median PFS was 14.3 months. 56.9% of patients experienced ≥ grade 3 TRAEs, such as hypertension (10.3%) and elevated liver enzymes (13.8%). No new safety signals were identified. Participants with low levels of serum PCT value had satisfactory prognoses. Conclusion: TACE combination with lenvatinib plus sintilimab is effective in treating HCC with IVC and/or RA TT. The toxicities were manageable, with no unexpected safety signals. The baseline levels of serum PCT might be the predictive biomarkers for the triple combination therapy.

Carbocistein improves airway remodeling in asthmatic mice.

BACKGROUND: The alleviating effects of carbocisteine (S-carboxymethylcysteine, SCMC) have been implicated in chronic obstructive pulmonary disease; however, very little is known about its mechanisms in asthma. In this study, we aimed to investigate the effects of SCMC on airway remodeling in asthmatic mice induced by ovalbumin (OVA). METHODS: The asthma mouse model was generated by OVA sensitization and stimulation and subsequently intervened by SCMC or dexamethasone. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected from each group of mice. The TGF-ß1 levels in BALF were measured by ELISA. Masson's staining was used to detect collagen fiber deposition in mouse airway tissues, while immunohistochemistry and RT-qPCR were conducted to examine the protein and mRNA expression of TGF-ß1 in mouse lung airway tissues, respectively. The correlation between TGF-ß1 mRNA expression and the area of collagen fiber deposition in airway tissues was analyzed by Pearson's correlation coefficient. RESULTS: The area of collagen fiber deposition in the airway tissues of asthmatic mice was significantly increased, while SCMC alleviated the collagen fiber deposition in the airway tissues. TGF-ß1 expression was significantly elevated in BALF and airway tissues of asthmatic mice, while SCMC inhibited TGF-ß1 expression. TGF-ß1 expression was significantly and positively correlated with collagen fiber deposition in mouse airway tissues. CONCLUSIONS: SCMC intervention improves collagen fiber deposition in airway tissues and inhibits TGF-ß1 expression in asthmatic mice.

Blood Biomarkers Predict Survival Outcomes in Patients with Hepatitis B Virus-Induced Hepatocellular Carcinoma Treated with PD-1 Inhibitors.

Purpose: To investigate the prognostic value of blood markers in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) treated with PD-1 inhibitors. Patients and Methods. We retrospectively collected and analyzed the clinicopathological data of 110 HBV-induced HCC patients treated with PD-1 inhibitors. Progression-free survival (PFS) and overall survival (OS) were scrutinized using Kaplan-Meier analysis and the log-rank test, and all potential risk factors were analyzed with univariate and multivariate Cox regression analyses. Results: The mean OS and PFS were 6.5 and 5.5 months, respectively. According to Kaplan-Meier survival curves, elevated systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) correlated with decreased OS and PFS (all P < 0.05), and low lymphocyte-to-monocyte ratio (LMR) correlated with decreased PFS and OS (all P < 0.05). Per multivariate Cox regression analyses, SII, PLR, and portal vein tumor thrombus (PVTT) correlated independently with PFS (all P < 0.05), whereas SII, PLR, NLR, and portal vein tumor thrombus (PVTT) correlated with OS (all P < 0.05). Conclusion: SII, PLR, and PVTT predicted OS and PFS in HCC patients who received PD-1 inhibitors and, therefore, could be useful predictors for risk stratification and individualized therapeutic decision-making for patients with HBV-induced HCC treated with PD-1 inhibitors.

Divergent Access to Polycyclic N-Heterocyclic Compounds through Büchner-Type Dearomatization Enabled Cycloisomerization of Diynamides under Gold Catalysis.

Catalytic dearomatization has been considered as a valuable approach to convert readily accessible flat molecules to products with three-dimensional frameworks. Herein, an unprecedented gold-catalyzed oxidative Büchner-type cyclopropanation is described that enables the cycloisomerization of diynamides. By variation of the position of substituents on the phenyl ring, a variety of fused N-heterocyclic products with challenging structural skeletons were obtained divergently.

New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Optomechanical squeezing with pulse modulation.

Quantum control technology provides an increasingly useful toolbox for quantum information tasks. In this Letter, by introducing a pulsed coupling to a standard optomechanical system, we show that stronger squeezing can be obtained with pulse modulation due to the reduction of the heating coefficient. Also, the general squeezed states, such as the squeezed vacuum, squeezed coherent, and squeezed cat states, can be obtained with their squeezing level exceeding 3 dB. Moreover, our scheme is robust to cavity decay, thermal temperature, and classical noise, which is friendly to experiments. The present work can extend the application of quantum engineering technology in optomechanical systems.

CalliSpheres drug-eluting beads transarterial-chemoembolization in the treatment of liver metastases from breast cancer: Initial experience in 14 patients.

ABSTRACT: Breast cancer patients with liver metastases are associated with high mortality. However, no standardized treatment approach is available for these patients who have undergone chemotherapy and hormonal therapy. We aimed to assess the clinical outcomes of patients with breast cancer liver metastases (BCLM) who underwent drug-eluting beads used for transarterial-chemoembolization (DEB-TACE).We retrospectively enrolled 14 patients with 39 lesions who underwent DEB-TACE for liver metastases following mastectomy for primary breast cancer. The incidence of complications, overall survival (OS), and local tumor progression-free survival (PFS) were assessed.A total of 14 patients with 39 liver metastases were treated with DEB-TACE from July 2017 to July 2020. The objective response rates (ORR) and disease control rates (DCR) were 71.4% and 92.8% at the 3-month period and 50% and 71.4% at the 6-month period, respectively. During the follow-up period the local tumor PFS was 8.0 months. The median OS was 20.0 months (range, 8-40 months) and the 1-, 2-year OS rates were 84.4% and 47.4%, respectively. No severe complications caused by this technique were detected.DEB-TACE for BCLM was characterized as a low trauma technique, with a limited number of complications. The results indicated that this method was safe and effective for patients with BCLM and could be widely adopted as a palliative treatment in clinical practice.

Improving few-photon optomechanical effects with coherent feedback.

Few-photon effects such as photon blockade and tunneling have potential applications in modern quantum technology. To enhance the few-photon effects in an optomechanical system, we introduce a coherent feedback loop to cavity mode theoretically. By studying the second-order correlation function, we show that the photon blockade effect can be improved with feedback. Under appropriate parameters, the photon blockade effect exists even when cavity decay rate is larger than the single-photon optomechanical coupling coefficient, which may reduce the difficulty of realizing single-photon source in experiments. Through further study of the third-order correlation function, we show that the tunneling effect can also be enhanced by feedback. In addition, we discuss the application of feedback on Schrödinger-cat state generation in an optomechanical system. The result shows that the fidelity of cat state generation can be improved in the presence of feedback loop.

Magnon-mediated nonreciprocal microwave transmission based on quantum interference.

Nonreciprocity has always been a subject of interest and plays a key role in a variety of applications like signal processing and noise isolation. In this work, we propose a simple and feasible scheme to implement nonreciprocal microwave transmission in a high-quality-factor superconducting cavity with ferrimagnetic materials. We derive necessary requirements to create nonreciprocity in our system where a magnon mode and two microwave modes are coupled to each other, highlighting the adjustability of a static magnetic field controlled nonreciprocal transmission based on quantum interference between different transmission paths, which breaks time-reversal symmetry of the three-mode cavity magnonics system. The high light isolation adjusted within a range of different magnetic fields can be obtained by modulating the photon-magnon coupling strength. Due to the simplicity of the device and the system tunability, our results may facilitate potential applications for light magnetic sensing and coherent information processing.

Trans-jugular intrahepatic portosystemic shunt in patients with hepatic cellular carcinoma: A preliminary study.

PURPOSE: To analyze the effects of trans-jugular intrahepatic portosystemic shunt (TIPS) on portal hypertension and liver function in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirteen patients with hemorrhage caused by portal hypertension and HCC who received TIPS and antitumor treatment were retrospectively analyzed. Trans-arterial chemoembolization, microwave ablation, target therapy, and immunetherapy or combined therapy were performed to treat HCC. Child-Pugh score was applied to estimate liver functions before and after TIPS. Shunting patency, overall survival (OS), and progression-free survival were analyzed. RESULTS: The median age was 58 (interquartile range: 52.5-62.5) years. The ratio with ascites before and after TIPS was 84.6% (11/13) and 7.7% (1/13), with P < 0.001. The ratio with Child-Pugh A before and after TIPS were 61.5% (8/13) and 84.6% (11/13) respectively, with P = 0.179. Mean portal vein pressure before and after TIPS was 27.85 ± 7.02 mmHg and 16.23 ± 6.61 mmHg, respectively, with P = 0.001. Two-year shunting patency rate was 61.5%. Median OS was 29.8 ± 11.5 months (95% confidence interval [CI] 22.8-36.7), and median progression-free survival was 20.2 ± 13.2 months (95% CI 12.2-28.1). CONCLUSION: TIPS could reduce ascites, down-regulate the Child-Pugh score, and give a chance for further anti-tumor therapy.

Prognostic and predictive significance of the tumor microenvironment in hepatocellular carcinoma.

BACKGROUND: Identification of molecular markers that reflect the characteristics of the tumor microenvironment (TME) may be beneficial to predict the prognosis of post-operative hepatocellular carcinoma (HCC) patients. OBJECTIVE AND METHODS: A total of 100 tissue samples from HCC patients were separately stained by immunohistochemistry to examine the expression levels of CD56, CD8α, CD68, FoxP3, CD31 and pan-Keratin. The prognostic values were analyzed by Cox regression and the Kaplan-Meier method. RESULTS: Univariate and multivariate logistic analysis showed that FoxP3 was the independent factor associated with microvascular invasion (MVI), tumor size and envelop invasion; CD68 was associated with envelope invasion and AFP. Kaplan-Meier survival curves revealed that CD68 and FoxP3 expression were significantly associated with relapse free survival (RFS) of HCC patients (P< 0.05). The ROC curve indicated that the combination of tumor number, MVI present and CD68 expression yielded a ROC curve area of 82.3% (86.36% specificity, 68.75% sensitivity) to evaluate the prognosis of HCC patients, which was higher than the classifier established by the combination of tumor number and MVI (78.8% probability, 63.64% specificity and 85.42% sensitivity). CONCLUSIONS: Our study indicated that CD68 and FoxP3 are associated with prognosis of HCC patients, and CD68 can be considered as a potential prognostic and predictive biomarker.

Effect of partial splenic embolization on transarterial chemoembolization for hepatocellular carcinoma with hypersplenism.

ABSTRACT: This study retrospectively studied transarterial chemoembolization (TACE) combined with partial splenic embolization (PSE) in the treatment of hepatocellular carcinoma (HCC) with severe hypersplenism.Seventy patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stage B or C with hypersplenism were divided into non-partial splenic embolization group (N-PSE, n = 51) and partial splenic embolization group (PSE, n = 19). The N-PSE group was further divided into N-PSE with mild to moderate hypersplenism (N-PSE-M, 47 cases) and N-PSE with severe hypersplenism (N-PSE-S, 4 cases).In the PSE group, leukocytes, neutrophils, lymphocytes, and platelets were significantly increased (P < .05) and were significantly different from that in the N-PSE group (P < .05). In the N-PSE group, except for a slight increase in neutrophils, other blood cells were decreased, including lymphocytes that were significantly decreased (P < .05). There was no significant difference in the changes of liver function between the 2 groups before and after surgery (P > .05). The analysis showed a significant increase in ascites after 6 months of TACE in the N-PSE group (P < .05). According to the follow-up results, the median overall survival (OS) in the PSE group was 24.47 ±â€Š3.68 (months) and progression-free survival (PFS) was 12.63 ±â€Š4.98 (months). Regardless of OS or PFS, the PSE group was superior to the N-PSE group and its subgroups, with a statistically significant difference in PFS between the N-PSE group and PSE group (P < .05). Moreover, the time of extrahepatic progression was significantly earlier in the N-PSE group than in the PSE group (P < .05). N-PSE-S group had the worst prognosis, and PFS and OS were worse than the other 2 groups, suggesting that PSE in severe hypersplenism may improve PFS and OS.In patients with HCC and severe hypersplenism, TACE should be actively combined with PSE treatment.

Type of Necrosis Influences Prognosis in Hepatocellular Carcinoma After the First Transarterial Chemoembolization.

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common tumors. Transarterial chemoembolization (TACE) is the first choice of treatment for intermediate HCC and an important treatment option for advanced HCC. This retrospective study compared the prognosis between patients showing coagulative necrosis and patients showing liquefactive necrosis after the first TACE procedure. MATERIAL AND METHODS We divided 171 patients with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC into 2 groups; a coagulative necrosis group (79 patients) and a liquefactive necrosis group (92 patients). The coagulative and liquefactive necroses were identified by computed tomography after the first TACE procedure. Kaplan-Meier analysis was used to identify the differences in the overall survival (OS) and progression-free survival (PFS) between the 2 groups, and the associated risk factors and safety of TACE were analyzed. RESULTS The median OS durations were 23.27±1.40 months and 8.83±2.15 months (P=0.004) and the median PFS durations were 9.33±0.96 months and 3.70±0.44 months (P=0.002) in the coagulative necrosis and liquefactive necrosis groups, respectively. Intrahepatic in situ progression, new intrahepatic metastasis, and extrahepatic progression occurred significantly earlier in the liquefactive necrosis group (P<0.05). Univariate analysis and multivariate analyses showed liquefactive necrosis was the main risk factor for OS. There was no significant difference in the hepatic function impairment or post-embolism syndrome after TACE. CONCLUSIONS After the first TACE procedure, the patients with liquefactive necrosis experienced recurrence and metastasis earlier and had a worse prognosis. Therefore, these patients should be considered for earlier administration of targeted therapies or immunotherapies after TACE.

N6-methyladenosine reader YTHDC2 and eraser FTO may determine hepatocellular carcinoma prognoses after transarterial chemoembolization.

Transarterial chemoembolization (TACE) has significantly improved overall survival (OS) of unresectable hepatocellular carcinoma (HCC) patients. Unfortunately, a portion of patients show no therapeutic responses to TACE. N6-methyladenosine (m6A) as well as its epigenetic writers, erasers, and readers play a crucial role in HCC development. However, it is still largely unclear how functional small nucleotide polymorphisms (SNPs) in m6A-regulating genes contribute to prognosis of TACE-treated HCC patients. In this study, potential functional SNPs were systematically evaluated to identify their roles in the prognosis of HCC patients after TACE in a Chinese Han population. Employing multiple databases, we successfully annotated 55 candidate SNPs. After genotyping these SNPs in our TACE cohort, we identified three genetic variants in YTHDC2 (rs6594732, rs10071816, and rs2303718) and one SNP in FTO (rs7202116) having statistically significant associations with the OS of HCC patients treated with TACE. For example, multivariate Cox proportional hazards model indicated that the rs7202116 GG genotype carriers had markedly shorter OS and an 87% increased death risk compared with the AA carriers after TACE therapy (P = 0.002). When investigating functional relevance of these SNPs, we observed an allelic regulation of rs7202116 on FTO expression in HCC tissue samples, with higher tumor suppressor FTO expression among the A allele carriers. Our findings reported the first evidence supporting the prognostic value of m6A reader YTHDC2 and m6A eraser FTO SNPs in TACE-treated HCC patients. Importantly, our data implicated that m6A-regulating genes may be targets to improve therapeutic strategy for unresectable HCC patients.

Gold-Catalyzed Oxidative Cascade Cyclization of 1,3-Diynamides: Polycyclic N-Heterocycle Synthesis via Construction of a Furopyridinyl Core.

A facile and practical approach to construct a furopyridinyl motif through a gold-catalyzed cascade cyclization of easily accessible diynamides is described. This strategy offers a straightforward approach to furo[2,3-c]isoquinoline and 6H-furo[3',2':5,6]pyrido[3,4-b]indole derivatives. The reaction could build up four new bonds and two additional heteroaromatic rings via a single operation. The heterocyclic products show promising blue luminous performance with fluorescence quantum yields up to 75%.

Silencing of lncRNA PVT1 by miR-214 inhibits the oncogenic GDF15 signaling and suppresses hepatocarcinogenesis.

The prognosis for hepatocellular carcinoma (HCC) is dismal. Long noncoding RNA PVT1 has been linked to malignancies and might be a deleterious therapy target. However, the key events controlling its expression in HCC remain undetermined. Here, we address how PVT1 is fine-regulated and its downstream signaling in hepatoma cells. Interestingly, we found that c-Myc and P53 could divergently regulate PVT1 transcription. Oncoprotein c-Myc enhances PVT1 expression, whereas P53 suppresses its expression. We also identified miR-214 as a crucial, negative regulator of PVT1. Consistently, high miR-214 levels were significantly correlated with diminished PVT1 expression in HCC specimens. Silencing of PVT1 by ectopic miR-214 or siRNAs markedly inhibited viability and invasion of HCC cells. In opposition, inhibition of endogenous miR-214 promoted PVT1 expression and enhanced cell proliferation. Notably, oncogenic GDF15 is a potential downstream target of the miR-214-PVT1 signaling. Collectively, our results show that the c-Myc/P53/miR-214-PVT1-GDF15 axis is implicated in HCC development, shedding light on the mechanistic actions of PVT1 and representing potential targets for HCC clinical intervention.