Highly Upregulated In Liver Cancer Research Articles

LPS promotes the progression of sepsis by activation of lncRNA HULC/miR-204-5p/TRPM7 network in HUVECs.

Sepsis is a systemic inflammatory response syndrome caused by infection. Lipopolysaccharide (LPS) has been reported to induce inflammatory responses, and long non-coding RNA highly up-regulated in liver cancer (HULC) expression was associated with the progression of sepsis. But the role and underlying mechanism of HULC in LPS-induced sepsis remain unclear. Cell viability and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry assays, respectively. The levels of apoptosis-related proteins, inflammatory cytokines and transient receptor potential melastatin7 (TRPM7) were detected by western blot. Reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by dichloro-dihydro-fluorescein diacetate (DCFH-DA) method using commercial kit. HULC, microRNA-204-5p (miR-204-5p) and TRPM7 expressions in serum of sepsis patients and human umbilical vein endothelial cells (HUVECs) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between HULC and miR-204-5p, miR-204-5p and TRPM7. LPS stimulation restrained cell viability and facilitated apoptosis, inflammatory injury and oxidative stress in HUVECs. HULC and TRPM7 were increased and accompanied with decreased miR-204-5p expression in serum of sepsis patients. A significant negative correlation between miR-204-5p and HULC or TRPM7 was observed, and there was a positive relationship between expressions of HULC and TRPM7. Importantly, LPS inhibited the cell viability and induced apoptosis, inflammatory injury and oxidative stress of HUVECs by up-regulating the expressions of HULC and TRPM7, and down-modulating miR-204-5p expression. Mechanically, HULC positively regulated TRPM7 expression by sponging miR-204-5p in HUVECs. LPS impaired cell viability, and promoted cell apoptosis, inflammatory response and oxidative stress in HUVECs by regulating HULC/miR-204-5p/TRPM7 axis.

Long Non-Coding HULC and miRNA-372 as Diagnostic Biomarkers in Hepatocellular Carcinoma.

We aimed to evaluate the effectiveness of Highly Upregulated in Liver Cancer (HULC) and microRNA-372 (miR-372) as biochemical markers in Hepatocellular carcinoma (HCC) and HCV-infected patients. The present study was conducted on 100 Egyptian individuals divided into 3 groups, 40 patients with HCC and HCV infection, 40 patients only HCV-infected, and 20 individuals as normal controls. They were subject to full history taking, full clinical and laboratory examination, and assessment of HULC and miR-372 levels by real-time PCR. A statistically significant difference was found with p< 0.05 between HCC and each of HCV and control groups as regards HULC level with high mean among HCC followed by HCV patients. Our results also show a statistically significant difference with p< 0.05 between each of HCC and HCV compared to control as regards miR-372 level with low mean among HCC patients. HULC could be considered as a potential non-invasive marker for detection and early diagnosis of HCC. Also, it may play an important role in the early prophylaxis and control measures to reduce the incidence of HCC. However, miR-372 cannot be considered as a reliable marker as HULC for early detection of HCC especially in HCV patients.

Highly upregulated in liver cancer (HULC): An update on its role in carcinogenesis.

Highly upregulated in liver cancer (HULC) was initially recognized during the screening of a hepatocellular carcinoma (HCC)-specific gene library. Further studies demonstrated its aberrant upregulation in several other tumor types. The oncogenic roles of this long noncoding RNA (lncRNA) have been verified through expression studies as well as functional studies. Moreover, the results of knockdown experiments have indicated diminished carcinogenic effects of cancer cell line in nude mice following HULC silencing. More recent studies have shown that expression levels of this lncRNA might be used as diagnostic biomarkers in cancer patients. Moreover, mechanistical studies have revealed associations between HULC and two HCC-related viruses namely hepatitis B and C viruses. Taken together, HULC can be regarded as a therapeutic target not only for HCC but also for a variety of human malignancies. In the current review, we summarized the recent literature about the role of HULC in the carcinogenesis and its potential application in cancer diagnosis and prognosis.

Association Between lncRNA HULC rs7763881 Polymorphism and Gastric Cancer Risk.

PurposeGastric cancer (GC) is one of the most common cancers in the world. Recently, several studies have suggested that single-nucleotide polymorphisms (SNPs) of long noncoding RNA (lncRNA) are associated with GC risk. However, the association of the lncRNA highly upregulated in liver cancer (HULC) SNP with GC risk is not yet known. The aims of this study were to evaluate the association between HULC rs7763881 SNP and the risk of GC and GC subgroups via a case–control study.Patients and Methodsrs7763881 was genotyped using TaqMan genotyping assay with 459 GC patients and 379 controls.ResultsA significant association between HULC rs7763881 SNP and GC risk was not found. However, after adjustment for age and gender, the rs7763881 recessive model (CC) showed a significant association with an increased GC risk in the undifferentiated (odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.17–2.94, P = 0.009), diffuse-type GC (OR = 1.72, 95% CI = 1.05–2.82, P = 0.033), LNM-positive (OR = 2.02, 95% CI = 1.24–3.27, P = 0.004), T3/T4 (OR = 1.75, 95% CI = 1.05–2.91, P = 0.032), and tumor stage III (OR = 2.01, 95% CI = 1.17–3.45, P = 0.011) subgroups when compared to the rs7763881 combined genotypes (AA+AC). Furthermore, after adjusting for age and gender, the rs7763881 additive model (CC) indicated a significantly higher GC risk than rs7763881 AA genotype in the undifferentiated (OR = 1.96, 95% CI = 1.15–3.32, P = 0.013), diffuse-type GC (OR = 2.08, 95% CI = 1.23–3.52, P = 0.004), and LNM-positive (OR = 2.00, 95% CI = 1.14–3.49, P = 0.016) subgroups.ConclusionOur findings suggest that the HULC rs7763881 SNP is associated with increased susceptibility to GC. However, further studies are required to validate our results in large populations as well as different ethnic groups.

&lt;p&gt;Long Non-Coding RNA HULC Promotes Cervical Cancer Cell Proliferation, Migration and Invasion via miR-218/TPD52 Axis&lt;/p&gt;

ObjectiveLong non-coding RNAs (lncRNAs) have been identified as important players in tumorigenesis. LncRNA highly upregulated in liver cancer (HULC) has been identified as a key regulator in the progression of various cancers. However, the functional role and the mechanisms of HULC in regulating cervical cancer cell behavior remain unclear.MethodsHULC expression, miR-218 expression and TPD52 mRNA level in cervical cancer cells were examined by qRT-PCR. Cell proliferation was evaluated by MTT assay. Cell migration and invasion were examined by Transwell assay. TPD52 protein level was measured by Western blot. Dual-luciferase reporter assay was measured to verify the combination of HULC and miR-218 as well as miR-218 and TPD52.ResultsHULC expression was upregulated in cervical cancer cell lines, and HULC promoted cervical cancer cell proliferation, migration and invasion. Mechanistically, HULC acted as a sponge of miR-218 to elevate expression of TPD52, a target of miR-218, and thereby promoted cervical cancer cell proliferation, migration, and invasion.ConclusionHULC promotes cervical cancer cell proliferation, migration and invasion via miR-218/TPD52 axis.

Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer.

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA‐related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA‐miRNA‐mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer‐specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA‐related DEmRNAs. According to the modularization of protein‐protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up‐regulated in liver cancer (HULC) and RP11‐314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11‐999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real‐time PCR. The findings from this study indicate that HULC, RP11‐314B1.2, LINC00106, and RP11‐999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.

Study of long non-coding RNA highly upregulated in liver cancer (HULC) in breast cancer: A clinical & in vitro investigation.

Background & objectives:Breast cancer remains the most common malignancy among women worldwide. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in tumour initiation and progression. This study was aimed to evaluate the potential role of lncRNA highly upregulated in liver cancer (HULC) in breast cancer.Methods:The expression of HULC was evaluated in breast cancer patients and cell lines using real-time quantitative reverse transcription polymerase chain reaction. Small interfering RNA-based knockdown was also employed to study the potential role of HULC in breast cancer cell lines including ZR-75-1, MCF7 and MDA-MB-231.Results:HULC was significantly upregulated in tumour tissues compared to non-tumoural margins (P<0.001). The receiver operating characteristic (ROC) curve analysis demonstrated the biomarker potential of HULC (ROCAUC=0.78, P<0.001). The HULC knockdown induced apoptosis and suppressed cellular migration in breast cancer cell lines.Interpretation & conclusions:Our results indicated that HULC was upregulated in breast cancer and might play a role in tumourigenesis. The HULC may have a potential to be exploited as a new biomarker and therapeutic target in breast cancer.

Long non-coding RNA HULC exerts oncogenic activity on papillary thyroid cancer in vitro and in vivo

Thyroid cancer is a frequently happened malignancy in human endocrine system. Papillary thyroid cancer (PTC) presents 70–80% of all thyroid cancer cases. Herein, we probed the possible oncogenic function of long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) in PTC. First, the HULC and microRNA-106a (miR-106a) expressions in PTC tissues and cells were tested. Plasmids or miRNAs transfections were done for altering HULC and miR-106a expressions. Then, cells viability and apoptosis, along with cell proliferative, migratory and invasive abilities, were tested, respectively. The PI3K/AKT and Wnt/β-catenin pathways activities were measured. Finally, the animal model of PTC was constructed and the tumour volumes and weights were gauged. We discovered that HULC and miR-106a had relative high expression levels in PTC tissues and cells. HULC overexpression enhanced TPC-1 cells viability and cell proliferative, migratory and invasive abilities. Silencing HULC induced TPC-1 cell apoptosis. miR-106a engaged in the oncogenic impacts of HULC. Moreover, HULC overexpression boosted PI3K/AKT and Wnt/β-catenin pathways activities via raising miR-106a expression. Besides, HULC overexpression enhanced the volumes and weights of PTC tumours. To sum up, HULC exhibited oncogenic function on PTC in vitro and in vivo.

Circulating extracellular vesicle-encapsulated HULC is a potential biomarker for human pancreatic cancer.

The role of long noncoding RNAs (lncRNAs) in the epithelial‐mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor‐β in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA‐133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV‐encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle‐transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA‐133b suppresses the EMT by targeting HULC. Extracellular vesicle‐encapsulated HULC could be a potential circulating biomarker for human PDAC.

LncRNA HULC promotes the progression of gastric cancer by regulating miR-9-5p/MYH9 axis

Long non-coding RNAs (lncRNAs) highly upregulated in liver cancer (HULC) has been identified as an oncogene involved in many human cancers. Herein, we aimed to further explore the role and molecular mechanism of HULC in gastric cancer (GC) progression. The levels of HULC, miR-9-5p and myosin heavy chain 9 (MYH9) mRNA were detected by qRT-PCR. The targeted interaction between HULC and miR-9-5p was verified by dual-luciferase reporter and RNA pull-down assays. Cell proliferation assay, cell colony formation, flow cytometry and transwell assay were used to determine cell proliferation, colony formation, apoptosis and migration and invasion, respectively. Xenograft assay was used to observe the effect of HULC on GC growth in vivo. Our results revealed that HULC was upregulated and miR-9-5p was downregulated in GC, and both were associated with clinicopathologic features of GC patients. A positive correlation was found between HULC expression and epithelial-to-mesenchymal transition (EMT) of GC tissues. Moreover, HULC repressed miR-9-5p expression by binding to miR-9-5p. The regulatory effects of HULC knockdown on GC cell proliferation, migration, invasion, EMT and apoptosis were reversed by introduction of anti-miR-9-5p. HULC regulated MYH9 expression by acting as a molecular sponge of miR-9-5p in GC cells. HULC knockdown inhibited tumor growth in vivo. In conclusion, our data demonstrated that HULC knockdown repressed GC progression at least partly by regulating miR-9-5p/MYH9 axis.

Long noncoding RNA HULC promotes hepatocellular carcinoma progression.

Long noncoding RNAs (lncRNAs) are overexpressed in many types of cancers, suggesting they may promote tumorigenesis. The lncRNA “highly upregulated in liver cancer” (HULC) promotes hepatocellular carcinoma (HCC) by mechanisms that are not fully understood. In the present study, we showed that HULC is overexpressed in HCC tissues, which correlates with an unfavorable prognosis in HCC patients. We also found that HULC promotes the proliferation, migration, and invasion of HCC cells in vitro, and xenograft tumor growth in vivo. Our mechanistic studies showed that HULC works as a competing endogenous RNA for miR-2052, and that the MET receptor tyrosine kinase is a downstream target of miR-2052 in HCC. Furthermore, HULC inhibits miR-2052, thereby stimulating MET expression in HCC. Finally, MET overexpression reverses the effects of HULC depletion. In sum, our findings reveal a novel regulatory signaling cascade, the HULC/miR-2052/MET axis, which could potentially be exploited for therapeutic benefits in the treatment of HCC.

Small molecule inhibition of Ewing sarcoma cell growth via targeting the long non coding RNA HULC.

Ewing sarcomas (ES) are aggressive pediatric cancers of bone and soft tissues characterized by in frame chromosomal translocations giving rise to chimeric transcription factors, such as EWS-FLI1. An emerging strategy to block EWS-FLI1 activity is represented by the small molecule YK-4-279, which binds to EWS-FLI1 and alters its transcriptional activity. The specific effectors of the anti-oncogenic activity of YK-4-279 are still largely unknown. Herein, by performing a high-throughput screening we identify the lncRNA HULC (Highly Upregulated in Liver Cancer) as a prominent target of YK-4-279 activity in ES cells. High levels of HULC correlate with ES aggressiveness, whereas HULC depletion reduces ES cell growth. Mechanistically, we find that HULC promotes the expression of TWIST1 oncogene by sponging miR-186. Downregulation of HULC upon treatment with YK-4-279 reduces the expression of TWIST1 by unleashing miR-186 and favoring its binding to TWIST1 transcripts. Notably, high levels of miR-186 and low levels of TWIST1 correlate with better prognosis in ES patients. Our results disclose a novel oncogenic regulatory circuit mediated by HULC lncRNA that is disrupted by the small molecule YK-4-279, with promising therapeutic implications for ES treatment.

Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion.

BACKGROUNDHighly upregulated in liver cancer (HULC) is a long non-coding RNA (lncRNA) which has recently been identified as a key regulator in hepatocellular carcinoma (HCC) progression. However, its role in the secretion of exosomes from HCC cells remains unknown.AIMTo explore the mechanism by which HULC promotes the secretion of exosomes from HCC cells.METHODSSerum and liver tissue samples were collected from 30 patients with HCC who had not received chemotherapy, radiotherapy, or immunotherapy before surgery. HULC expression in serum exosomes and liver cancer tissues of patients was measured, and compared with the data obtained from healthy controls and tumor adjacent tissues. The effect of HULC upregulation in HCC cell lines and the relationship between HULC and other RNAs were studied using qPCR and dual-luciferase reporter assays. Nanoparticle tracking analysis was performed to detect the quantity of exosomes.RESULTSHULC expression in serum exosomes of patients with HCC was higher than that in serum exosomes of healthy controls, and HULC levels were higher in liver cancer tissues than in tumor adjacent tissues. The expression of HULC in serum exosomes and liver cancer tissues correlated with the tumor-node-metastasis (TNM) classification, and HULC expression in tissues correlated with that in serum exosomes. Upregulation of HULC promoted HCC cell growth and invasion and repressed apoptosis. Notably, it also facilitated the secretion of exosomes from HCC cells. Moreover, qPCR assays showed that HULC repressed microRNA-372-3p (miR-372-3p) expression. We also identified Rab11a as a downstream target of miR-372-3p. Dual-luciferase reporter assays suggested that miR-372-3p could directly bind both HULC and Rab11a.CONCLUSIONOur findings illustrate the importance of the HULC/miR-372-3p/Rab11a axis in HCC and provide new insights into the molecular mechanism regulating the secretion of exosomes from HCC cells.

LncRNA HULC promotes lung squamous cell carcinoma by regulating PTPRO via NF-κB.

Accumulating studies have implicated that long noncoding RNA (lncRNA) plays a vital role in lung cancer. However, little is known of the role of lncRNA highly upregulated in liver cancer (HULC) in the pathogenesis of lung squamous cell carcinoma (LSCC). In this study, we investigated the modifying effects and underlying mechanisms of lncRNA HULC in LSCC. Significantly decreased level of lncRNA HULC was observed in LSCC samples compared with adjacent tissues. Besides, the expression of lncRNA HULC was negatively associated with protein tyrosine phosphatase receptor type O (PTPRO) in LSCC. Moreover, lncRNA HULC could promote the proliferation of LSCC cells by downregulating the expression PTPRO dependent on the phosphorylation and activation of nuclear factor-κB (NF-κB). The present study firstly shows strong evidence supporting a critical role of lncRNA HULC in promoting LSCC by regulating PTPRO/NF-κB signaling pathway, which provides new promising biomarkers for LSCC.

Hepatocellular carcinoma up-regulated long non-coding RNA: a putative marker in multiple sclerosis.

Highly up-regulated in liver cancer (HULC) is a cancer-associated long non-coding RNA (lncRNA) which may regulate expression of other genes by working as a competing RNA for microRNAs. In the current study, we assessed transcript levels of this lncRNA in peripheral blood of multiple sclerosis (MS) patients and healthy persons to evaluate its possible role in the pathogenesis of this inflammatory disease and its diagnostic power. The results of Multilevel Bayesian showed no significant difference between cases and controls (P = 0.002, 95% confidence interval (CI) = [3.08, 13.3]). However, based on the results of Quantile regression, there was a significant difference in HULC expression between cases and controls after controlling the effects of sex and age (P = 0.002, 95% CI = [3.08, 13.3]) which shows different trends in males and females. HULC expression was inversely correlated with age of male subjects but not female subjects. HULC transcript levels had 91.1% accuracy in diagnosis of MS disease (Specificity: 80%, Sensitivity: 86.6%). The diagnostic power of HULC was higher in male subjects aged less than 50years (AUC = 0.923, Specificity: 80%, Sensitivity: 100%). The present study shows the possibility of application of transcript levels of HULC as diagnostic marker in MS disease. However, future studies with larger sample sizes are necessary to validate our results.

Expression of long noncoding RNAs in breast cancer in relation to reproductive factors and tumor characteristics.

Long noncoding RNAs (lncRNA) regulate expressions of several cancer-related genes and pathways. Expression profiling of lncRNAs would pave the way for identification of dysregulated pathways in cancer. We assessed expression of FAS-anti sense 1 (FAS-AS1), Taurine Upregulated 1 (TUG1), OPA-interacting protein 5-AS1 (OIP5 -AS1), nuclear-enriched abundant transcript 1 (NEAT1), and highly upregulated in liver cancer (HULC) in breast tumor tissues and adjacent noncancerous tissues (ANCTs). TUG1 was downregulated in tumoral tissues. We found associations between TUG1 expression and mitotic rate, NEAT1 expression and breast feeding duration as well as FAS-AS1 and OPI5 expressions and menarche age. A combination of transcript levels of all genes had 88.5% sensitivity and 42.3% specificity in breast cancer diagnosis. The current study provides evidence for the contribution of lncRNAs in breast cancer in relation to reproductive factors and tumor characteristics.

HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p.

The aberrant expression of highly upregulated in liver cancer (HULC) has been reported to participate in ovarian cancer development. A recent research has revealed that HULC-modulated microRNAs (miRNAs) in tumorigenesis. To confirm the functions of HULC on tumorigenesis of ovarian, we explored the effects of HULC expression on ovarian cancer cell development, as well as the underlying mechanism. We transfected SKOV3 cells with pEX-HULC, sh-HULC, and miR-125a-3p mimic as well as their corresponding negative controls (pEX-3, sh-NC, and NC) to alter the expression of HULC and miR-125a-3p, which were analyzed by quantitative reverse transcription PCR (qRT-PCR). Expression of proteins associated with cell cycle, apoptosis, and signaling pathways was determined by Western blot assay. The proliferation, apoptosis, migration, and invasion were explored by bromodeoxyuridine (BrdU) incorporation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) method, and transwell migration and invasion assays, respectively. HULC overexpression promoted proliferation, migration, and invasion, while inhibited apoptosis of SKOV3 cells. In addition, HULC negatively regulated the expression of miR-125a-3p. Besides, miR-125a-3p mimic reversed the effects of HULC on proliferation, migration, and invasion as well as apoptosis of SKOV3 cells. Moreover, we found that HULC enhanced phosphorylated expression of regulatory factors in phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of rapamycin (PI3K/AKT/mTOR) signaling pathway by downregulating expression of miR-125a-3p. Overexpression of HULC promoted ovarian carcinoma development by activating PI3K/AKT/mTOR signaling pathway via downregulating miR-125a-3p.

Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy that exhibits high incidence worldwide. In diverse human cancers, the long non‐coding RNA (lncRNA) highly up‐regulated in liver cancer (HULC) is aberrantly expressed, but how HULC affects OSCC development and progression has remained mostly unknown. We report that HULC was abnormally up‐regulated in oral cancer tissues and OSCC cell lines, and that suppression of HULC expression in OSCC cells not only inhibited the proliferation, drug tolerance, migration and invasion of the cancer cells, but also increased their apoptosis rate. Notably, in a mouse xenograft model, HULC depletion reduced tumorigenicity and inhibited the epithelial‐to‐mesenchymal transition process. Collectively, our findings reveal a crucial role of the lncRNA HULC in regulating oral cancer carcinogenesis and tumour progression, and thus suggest that HULC could serve as a novel therapeutic target for OSCC.

Involvement of long non-coding RNA HULC (highly up-regulated in liver cancer) in pathogenesis and implications for therapeutic intervention

ABSTRACTIntroduction: HULC (highly upregulated in liver cancer) is a long non-coding RNA (lncRNA) which is, as its name suggests, highly upregulated in hepatocellular carcinoma and in several other cancers. Increased HULC expression levels are strongly associated with clinicopathologic features such as tumor stages and overall survival and is a driver of tumor proliferation, migration, and invasion.Areas covered: This review addresses the discovery of HULC and discusses the consequences of HULC deregulation in cancer, the underlying molecular mechanisms and the potential of HULC as a biomarker and therapeutic target.Expert opinion: HULC is a promising candidate as a therapeutic target in cancer; however, more studies are necessary to further elucidate the underlying molecular mechanism(s), especially in cancer types other than hepatocellular carcinomas. Future studies that focus on an optimized HULC-targeting approach are necessary to clarify the best strategy to target this lncRNA in vivo and in patients.Trial registration: ClinicalTrials.gov identifier: NCT02641847.Trial registration: ClinicalTrials.gov identifier: NCT03469544.Trial registration: ClinicalTrials.gov identifier: NCT03057171.Trial registration: ClinicalTrials.gov identifier: NCT02948855.Trial registration: ClinicalTrials.gov identifier: NCT03000764.Trial registration: ClinicalTrials.gov identifier: NCT02221999.

Effect of lncRNA HULC knockdown on rat secreting pituitary adenoma GH3 cells.

Pituitary adenoma is one of the most common tumors in the neuroendocrine system. This study investigated the effects of long non-coding RNAs (lncRNAs) highly up-regulated in liver cancer (HULC) on rat secreting pituitary adenoma GH3 cell viability, migration, invasion, apoptosis, and hormone secretion, as well as the underlying potential mechanisms. Cell transfection and qRT-PCR were used to change and measure the expression levels of HULC, miR-130b, and FOXM1. Cell viability, migration, invasion, and apoptosis were assessed using trypan blue staining assay, MTT assay, two-chamber transwell assay, Guava Nexin assay, and western blotting. The concentrations of prolactin (PRL) and growth hormone (GH) in culture supernatant of GH3 cells were assessed using ELISA. The targeting relationship between miR-130b and FOXM1 was verified using dual luciferase activity. Finally, the expression levels of key factors involved in PI3K/AKT/mTOR and JAK1/STAT3 pathways were evaluated using western blotting. We found that HULC was highly expressed in GH3 cells. Overexpression of HULC promoted GH3 cell viability, migration, invasion, PRL and GH secretion, as well as activated PI3K/AKT/mTOR and JAK1/STAT3 pathways. Knockdown of HULC had opposite effects and induced cell apoptosis. HULC negatively regulated the expression of miR-130b, and miR-130b participated in the effects of HULC on GH3 cells. FOXM1 was a target gene of miR-130b, which was involved in the regulation of GH3 cell viability, migration, invasion, and apoptosis, as well as PI3K/AKT/mTOR and JAK1/STAT3 pathways. In conclusion, HULC tumor-promoting roles in secreting pituitary adenoma might be via down-regulating miR-130b, up-regulating FOXM1, and activating PI3K/AKT/mTOR and JAK1/STAT3 pathways.