Kaempferol 3-Rhamnoside on Glutamate Release from Rat Cerebrocortical Nerve Terminals Involves P/Q-Type Ca2+ Channel and Ca2+/Calmodulin-Dependent Protein Kinase II-Dependent Pathway Suppression.

Excess synaptic glutamate release has pathological consequences, and the inhibition of glutamate release is crucial for neuroprotection. Kaempferol 3-rhamnoside (KR) is a flavonoid isolated from Schima superba with neuroprotective properties, and its effecton the release of glutamate from rat cerebrocortical nerve terminals was investigated. KR produced a concentration-dependent inhibition of 4-aminopyridine (4-AP)-evoked glutamate release with half-maximal inhibitory concentration value of 17 µM. The inhibition of glutamate release by KR was completely abolished by the omission of external Ca2+ or the depletion of glutamate in synaptic vesicles, and it was unaffected by blocking carrier-mediated release. In addition, KR reduced the 4-AP-evoked increase in Ca2+ concentration, while it did not affect 4-AP-evoked membrane potential depolarization. The application of selective antagonists of voltage-dependent Ca2+ channels revealed that the KR-mediated inhibition of glutamate release involved the suppression of P/Q-type Ca2+ channel activity. Furthermore, the inhibition of release was abolished by the calmodulin antagonist, W7, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN62, but not by the protein kinase A (PKA) inhibitor, H89, or the protein kinase C (PKC) inhibitor, GF109203X. We also found that KR reduced the 4-AP-induced increase in phosphorylation of CaMKII and its substrate synapsin I. Thus, the effect of KR on evoked glutamate release is likely linked to a decrease in P/Q-type Ca2+ channel activity, as well as to the consequent reduction in the CaMKII/synapsin I pathway.

Damage Detection of Regular Civil Buildings Using Modified Multi-Scale Symbolic Dynamic Entropy.

Based on the examination of the fundamental characteristics of structures, structural health monitoring (SHM) has received increased attention in recent years. Studies have shown that the SHM method using entropy analysis can precisely identify the damaged location of the structure, which is very helpful for the daily inspection or maintenance of civil structures. Although entropy analysis has shown excellent accuracy, it still consumes too much time and too many resources in terms of data processing. To improve the dilemma, in this study, modified multi-scale symbolic dynamic entropy (MMSDE) is adopted to identify the damaged location of the civil structure. A damage index (DI) based on the entropy diagram is also proposed to clearly indicate the damage location. A seven-story numerical model was created to verify the efficiency of the proposed SHM system. The results of the analysis of each case of damage show that the MMSDE curve for the damaged floor is lower than that for the healthy floor, and the structural damage can be correctly diagnosed by the damage index. Subsequently, a scaled-down steel benchmark experiment, including 15 damage cases, was conducted to verify the practical performance of the SHM system. The confusion matrix was used to further evaluate the SHM system. The results demonstrated that the MMSD-based system can quickly diagnose structural safety with reliability and accuracy. It can be used in the field of long-term structural health monitoring in the near future.

Verification of a Stiffness-Variable Control System with Feed-Forward Predictive Earthquake Energy Analysis.

Semi-active isolation systems with controllable stiffness have been widely developed in the field of seismic mitigation. Most systems with controllable stiffness perform more robustly and effectively for far-field earthquakes than for near-fault earthquakes. Consequently, a comprehensive system that provides comparable reductions in seismic responses to both near-fault and far-field excitations is required. In this regard, a new algorithm called Feed-Forward Predictive Earthquake Energy Analysis (FPEEA) is proposed to identify the ground motion characteristics of and reduce the structural responses to earthquakes. The energy distribution of the seismic velocity spectrum is considered, and the balance between the kinetic energy and potential energy is optimized to reduce the seismic energy. To demonstrate the performance of the FPEEA algorithm, a two-degree-of-freedom structure was used as the benchmark in the numerical simulation. The peak structural responses under two near-fault and far-field earthquakes of different earthquake intensities were simulated. The isolation layer displacement was suppressed most by the FPEEA, which outperformed the other three control methods. Moreover, superior control on superstructure acceleration was also supported by the FPEEA. Experimental verification was then conducted with shaking table test, and the satisfactory performance of the FPEEA on both isolation layer displacement and superstructure acceleration was demonstrated again. In summary, the proposed FPEEA has potential for practical application to unexpected near-fault and far-field earthquakes.

The Artificial Intelligence of Things Sensing System of Real-Time Bridge Scour Monitoring for Early Warning during Floods.

Scour around bridge piers remains the leading cause of bridge failure induced in flood. Floods and torrential rains erode riverbeds and damage cross-river structures, causing bridge collapse and a severe threat to property and life. Reductions in bridge-safety capacity need to be monitored during flood periods to protect the traveling public. In the present study, a scour monitoring system designed with vibration-based arrayed sensors consisting of a combination of Internet of Things (IoT) and artificial intelligence (AI) is developed and implemented to obtain real-time scour depth measurements. These vibration-based micro-electro-mechanical systems (MEMS) sensors are packaged in a waterproof stainless steel ball within a rebar cage to resist a harsh environment in floods. The floodwater-level changes around the bridge pier are performed using real-time CCTV images by the Mask R-CNN deep learning model. The scour-depth evolution is simulated using the hydrodynamic model with the selected local scour formulas and the sediment transport equation. The laboratory and field measurement results demonstrated the success of the early warning system for monitoring the real-time bridge scour-depth evolution.

Composite Multiscale Cross-Sample Entropy Analysis for Long-Term Structural Health Monitoring of Residential Buildings.

This study proposesd a novel, entropy-based structural health monitoring (SHM) system for measuring microvibration signals generated by actual buildings. A structural health diagnosis interface was established for demonstration purposes. To enhance the reliability and accuracy of entropy evaluation at various scales, composite multiscale cross-sample entropy (CMSCE) was adopted to increase the number of coarse-grained time series. The degree of similarity and asynchrony between ambient vibration signals measured on adjacent floors was used as an in-dicator for structural health assessment. A residential building that has been monitored since 1994 was selected for long-term monitoring. The accumulated database, including both the earthquake and ambient vibrations in each seismic event, provided the possibility to evaluate the practicability of the CMSCE-based method. Entropy curves obtained for each of the years, as well as the stable trend of the corresponding damage index (DI) graphs, demonstrated the relia-bility of the proposed SHM system. Moreover, two large earthquake events that occurred near the monitoring site were analyzed. The results revealed that the entropy values may have been slightly increased after the earthquakes. Positive DI values were obtained for higher floors, which could provide an early warning of structural instability. The proposed SHM system is highly stable and practical.

Performance Evaluation of an Entropy-Based Structural Health Monitoring System Utilizing Composite Multiscale Cross-Sample Entropy.

The aim of this study was to develop an entropy-based structural health monitoring system for solving the problem of unstable entropy values observed when multiscale cross-sample entropy (MSCE) is employed to assess damage in real structures. Composite MSCE was utilized to enhance the reliability of entropy values on every scale. Additionally, the first mode of a structure was extracted using ensemble empirical mode decomposition to conduct entropy analysis and evaluate the accuracy of damage assessment. A seven-story model was created to validate the efficiency of the proposed method and the damage index. Subsequently, an experiment was conducted on a seven-story steel benchmark structure including 15 damaged cases to compare the numerical and experimental models. A confusion matrix was applied to classify the results and evaluate the performance over three indices: accuracy, precision, and recall. The results revealed the feasibility of the modified structural health monitoring system and demonstrated its potential in the field of long-term monitoring.

The Long Non-Coding RNA MIR503HG Enhances Proliferation of Human ALK-Negative Anaplastic Large-Cell Lymphoma.

Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma. Currently, only a few gene rearrangements have been linked to ALK-negative ALCL progression. However, the specific molecular mechanisms underlying the growth of ALK-negative ALCL tumors remain unclear. Here, we investigated aberrantly expressed, long non-coding RNAs (lncRNAs) in ALK-negative ALCL and assessed their potential biological function. MIR503HG (miR-503 host gene) was highly expressed in ALK-negative cell lines and was significantly upregulated in tumors in mice formed from ALK-negative ALCL cell lines. Depletion of MIR503HG suppressed tumor cell proliferation in vivo and in vitro; conversely, its overexpression enhanced tumor cell growth. MIR503HG-induced proliferation was mediated by the induction of microRNA-503 (miR-503) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-ß receptor (TGFBR) and enhanced tumor cell growth. Collectively, these findings support a potential role for MIR503HG in cancer cell proliferation through the miR-503/Smurf2/TGFBR axis and indicate that MIR503HG is a potential marker in ALK-negative ALCL.

Entropy-Based Structural Health Monitoring System for Damage Detection in Multi-Bay Three-Dimensional Structures.

In this paper, a structural health monitoring (SHM) system based on multi-scale cross-sample entropy (MSCE) is proposed for detecting damage locations in multi-bay three-dimensional structures. The location of damage is evaluated for each bay through MSCE analysis by examining the degree of dissimilarity between the response signals of vertically-adjacent floors. Subsequently, the results are quantified using the damage index (DI). The performance of the proposed SHM system was determined in this study by performing a finite element analysis of a multi-bay seven-story structure. The derived results revealed that the SHM system successfully detected the damaged floors and their respective directions for several cases. The proposed system provides a preliminary assessment of which bay has been more severely affected. Thus, the effectiveness and high potential of the SHM system for locating damage in large and complex structures rapidly and at low cost are demonstrated.

Integration of High-Resolution Laser Displacement Sensors and 3D Printing for Structural Health Monitoring.

This paper presents a novel experimental design for complex structural health monitoring (SHM) studies achieved by integrating 3D printing technologies, high-resolution laser displacement sensors, and multiscale entropy SHM theory. A seven-story structure with a variety of composite bracing systems was constructed using a dual-material 3D printer. A wireless Bluetooth vibration speaker was used to excite the ground floor of the structure, and high-resolution laser displacement sensors (1-µm resolution) were used to monitor the displacement history on different floors. Our results showed that the multiscale entropy SHM method could detect damage on the 3D-printed structures. The results of this study demonstrate that integrating 3D printing technologies and high-resolution laser displacement sensors enables the design of cheap, fast processing, complex, small-scale civil structures for future SHM studies. The novel experimental design proposed in this study provides a suitable platform for investigating the validity and sensitivity of SHM in different composite structures and damage conditions for real life applications in the future.

Corpus callosum involvement and postoperative outcomes of patients with gliomas.

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

Ursolic acid inhibits the synaptic release of glutamate and prevents glutamate excitotoxicity in rats.

The present study evaluated the effect of ursolic acid, a natural pentacyclic triterpenoid, on glutamate release in rat cortical nerve terminals (synaptosomes) and its neuroprotection in a kainic acid-induced excitotoxicity rat model. In cortical synaptosomes, ursolic acid produced a concentration-dependent inhibition of evoked glutamate release with a half-maximum inhibition of release value of 9.5 µM, and calcium-free medium and the P/Q -type Ca2+ channel blocker, ω-agatoxin IVA, but not ω-conotoxin GVIA, an N-type Ca2+ channel blocker, prevented the ursoloic acid effect. The molecular docking study indicated that ursolic acid interacted with P/Q-type Ca2+ channels. Ursolic acid also significantly decreased the depolarization-induced activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the subsequent phosphorylation of synapsin I, and the ursolic acid effect on evoked glutamate release was inhibited by the CaMKII inhibitor KN 62 in synaptosomes. In addition, in rats that were intraperitoneally injected with ursolic acid 30 min before kainic acid intraperitoneal injection, cortical neuronal degeneration was attenuated. This effect of ursolic acid in the improvement of kainic acid-induced neuronal damage was associated with the reduction of kainic acid-induced glutamate increase in the cortex of rats; this was characterized by the reduction of glutamate and glutaminase levels and elevation of glutamate dehydrogenase, glutamate transporter 1, glutamate-aspartate transporter, and glutamine synthetase protein levels. These results suggest that ursolic acid inhibits glutamate release from cortical synaptosomes by decreasing P/Q-type Ca2+ channel activity and subsequently suppressing CaMKII and exerts a preventive effect against glutamate neurotoxicity by controlling glutamate levels.

17ß-Estradiol attenuates secondary injury through activation of Akt signaling via estrogen receptor alpha in rat brain following subarachnoid hemorrhage.

BACKGROUND: Apoptosis is implicated in vasospasm and the long-term sequelae of subarachnoid hemorrhage (SAH). This study tested the hypothesis that attenuation of SAH-induced apoptosis after 17ß-estradiol (E2) treatment is associated with an increase in phosphorylation of Akt via estrogen receptor-α (ER-α) in rats. MATERIALS AND METHODS: We examined the expression of phospho-Akt, ERα and ERß, and apoptosis in cerebral cortex, hippocampus, and dentate gyrus in a two-hemorrhage SAH model in rats. We subcutaneously implanted other rats with a silicone rubber tube containing E2; they received daily injections of nonselective estrogen receptor antagonist (ICI 182,780), selective ERα-selective antagonist (methyl-piperidino-pyrazole), or ERß-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. RESULTS: At 7 d after the first SAH, protein levels of phospho-Akt and ERα were significantly decreased and caspase-3 was significantly increased in the dentate gyrus. The cell death assay revealed that DNA fragmentation was significantly increased in the dentate gyrus. Those actions were reversed by E2 and blocked by ICI 182,780 and methyl-piperidino-pyrazole, but not R,R-tetrahydrochrysene. However, there were no significant changes in the expression of the protein levels of phospho-Akt, ERα, ERß, and caspase-3, and DNA fragmentation after SAH. CONCLUSIONS: The present study shows that a beneficial effect of E2 in attenuating SAH-induced apoptosis is associated with activation of the expression of phospho-Akt and ERα, and alteration in caspase-3 protein expression via an ERα-dependent mechanism in the dentate gyrus. These data support further the investigation of E2 in the treatment of SAH in humans.

Factors associated with poor outcome in patients with major intraoperative rupture of intracranial aneurysm.

PURPOSE: This clinical study was conducted to evaluate factors affecting outcome in the cases following major intraoperative rupture (MIOR) of the intracranial aneurysms. METHODS: Thirty cases with MIOR in a series of 467 surgeries for ruptured aneurysms were enrolled in this study. Clinical parameters, including: age, Hunt-Hess grading, Fisher grading, aneurysm size, aneurysm contour, operative timing, aneurysm location, and rupture timing were studied and compared with the prognosis in this particular cohort. The outcome was evaluated using the Glasgow Outcome Scale at least 3 months after surgery. Severe disability, vegetative survival, and death were classified as poor outcome. RESULTS: Among the 30 cases with MIOR, 11 resulted in poor outcomes (36.7%). Age was an important prognostic factor in this cohort. Those patients with poor outcome after MIOR were significantly older than those with good outcome (mean age: 64.6 vs 51.4 years, P=0.006). In this study, a trend toward poor outcome was observed in cases with MIOR on internal carotid artery aneurysms (8/14, 57.1% vs 2/9, 22.2% and 1/6, 16.7% on middle cerebral artery and anterior communicating artery aneurysms, P=0.197, after adjustment for age factor). There was a higher incidence of a poor outcome when MIOR occurred during clip application (5/6, 83.3% vs 1/5, 20.0% and 5/19, 26.3% when MIOR happened during brain retraction and aneurysm dissection, P=0.041 after adjustment with the factor of age). CONCLUSION: Although a larger sample population is required for a more conclusive result, MIOR occuring in older age, during clip application, or on an internal carotid artery aneurysm possibly has the trend to bear a worse outcome in the cohort of patients with MIOR during aneurysm surgery.

Metamaterials of Auxetic Geometry for Seismic Energy Absorption.

The propagation of earthquake energy occurs primarily through elastic waves. If the seismic force input to a structure can be directly reduced from the source, then the structure can be protected from seismic wave energy. Seismic metamaterials, regarded as periodic structures with properties different from conventional materials, use wave propagation characteristics and bandgaps to dissipate seismic wave energy. When the seismic wave is located in the bandgap, the transmission of seismic wave energy is effectively reduced, which protects the structure from the damage caused by seismic disturbance. In practical application, locating seismic frequencies below ten Hz is a challenge for seismic metamaterials. In the commonly used method, high-mass materials are employed to induce the effect of local resonance, which is not economically feasible. In this study, a lightweight design using auxetic geometry is proposed to facilitate the practical feasibility of seismic metamaterials. The benefits of this design are proven by comparing conventional seismic metamaterials with metamaterials of auxetic geometry. Different geometric parameters are defined using auxetic geometry to determine the structure with the best bandgap performance. Finite element simulations are conducted to evaluate the vibration reduction benefits of auxetic seismic metamaterials in time and frequency domains. Additionally, the relationship between the mass and stiffness of the unit structure is derived from the analytical solution of one-dimensional periodic structures, and modal analysis results of auxetic metamaterials are verified. This study provides seismic metamaterials that are lightweight, small in volume, and possess low-frequency bandgaps for practical applications.

Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer.

Liver cancer is one of the most lethal cancers in the world, mainly owing to the lack of effective means for early monitoring and treatment. Accordingly, there is considerable research interest in various clinically applicable methods for addressing these unmet needs. At present, the most commonly used biomarker for the early diagnosis of liver cancer is alpha-fetoprotein (AFP), but AFP is sensitive to interference from other factors and cannot really be used as the basis for determining liver cancer. Treatment options in addition to liver surgery (resection, transplantation) include radiation therapy, chemotherapy, and targeted therapy. However, even more expensive targeted drug therapies have a limited impact on the clinical outcome of liver cancer. One of the big reasons is the rapid emergence of drug resistance. Therefore, in addition to finding effective biomarkers for early diagnosis, an important focus of current discussions is on how to effectively adjust and select drug strategies and guidelines for the treatment of liver cancer patients. In this review, we bring this thought process to the drug resistance problem faced by different treatment strategies, approaching it from the perspective of gene expression and molecular biology and the possibility of finding effective solutions.

Effects of Thyroid Hormones on Lipid Metabolism Pathologies in Non-Alcoholic Fatty Liver Disease.

The typical modern lifestyle contributes to the development of many metabolic-related disorders, as exemplified by metabolic syndrome. How to prevent, resolve, or avoid subsequent deterioration of metabolic disturbances and the development of more serious diseases has become an important and much-discussed health issue. Thus, the question of the physiological and pathological roles of thyroid hormones (THs) in metabolism has never gone out of fashion. Although THs influence almost all organs, the liver is one of the most important targets as well as the hub of metabolic homeostasis. When this homeostasis is out of balance, diseases may result. In the current review, we summarize the common features and actions of THs, first focusing on their effects on lipid metabolism in the liver. In the second half of the review, we turn to a consideration of non-alcoholic fatty liver disease (NAFLD), a disease characterized by excessive accumulation of fat in the liver that is independent of heavy alcohol consumption. NAFLD is a growing health problem that currently affects ~25% of the world's population. Unfortunately, there are currently no approved therapies specific for NAFLD, which, if left uncontrolled, may progress to more serious diseases, such as cirrhosis or liver cancer. This absence of effective treatment can also result in the development of non-alcoholic steatohepatitis (NASH), an aggressive form of NAFLD that is the leading cause of liver transplantation in the United States. Because THs play a clear role in hepatic fat metabolism, their potential application in the prevention and treatment of NAFLD has attracted considerable research attention. Studies that have investigated the use of TH-related compounds in the management of NAFLD are also summarized in the latter part of this review. An important take-home point of this review is that a comprehensive understanding of the physiological and pathological roles of THs in liver fat metabolism is possible, despite the complexities of this regulatory axis-an understanding that has clinical value for the specific management of NAFLD.

LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression.

Tumor metastasis is a complex process modulated by both intrinsic and extrinsic factors that ultimately result in poorer patient outcomes, including diminished survival. Pseudogene-derived long non-coding RNAs (lncRNA) play important roles in cancer progression. In the current study, we found that the pseudogene-derived lncRNA LPAL2 is downregulated in hepatocellular carcinoma (HCC) tissues, and further showed that elevated LPAL2 expression is positively correlated with survival outcome. The knockdown of LPAL2 in hepatoma cells induced tumor formation, migration, invasion, sphere formation, and drug resistance. Metalloproteinase 9 (MMP9) was identified as an LPAL2-regulated target gene, consistent with clinical findings that LPAL2 expression is significantly associated with MMP9 expression. Furthermore, patients with a higher expression of LPAL2 and lower expression of MMP9 (LPAL2-high/MMP9-low) had a higher survival rate than those with other combinations. Collectively, our findings establish LPAL2 as a novel tumor suppressor in HCC, and suggest targeting LPAL2 and MMP9 as a therapeutic approach for the treatment of HCC.

A concise guideline for the management of large hemispheric infarction in Taiwan: 2010 update: a guideline from the Taiwan Stroke Society.

In this report, we present comprehensive recommendations for the diagnosis and treatment of large hemispheric infarction (LHI). A systematic literature search was conducted until June 30, 2010. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation (Table 1). The guideline was revised after several official meetings with local experts, and was reviewed by 3 expert reviewers. Early diagnosis of malignant large hemispheric infarction (MLHI) is critical. Studies have shown that using computed tomography (CT) or transcranial sonography to track midline shifting of the cerebrum and applying diffusion-weighted magnetic resonance imaging might contribute to the early recognition of MLHI. Glycerol and mannitol should be administered only when a patient shows evidence of brain edema or mass effect. The effect of barbiturate coma on improving prognosis is inconclusive and requires close monitoring of the patient. Meanwhile, using steroids on patients with stroke is not recommended. The effect of hyperventilation on reducing intracranial pressure is rapid but short-lived, and is used only in emergency situations. The target levels of PaCO2 are 30-35 mmHg. Moderate hypothermia (32-34°C) may be effective in controlling intracranial hypertension, but should be used cautiously along with rigorous monitoring. Timely decompressive craniectomy can probably offer patients a better chance of survival and quality of life. Usually, surgery for MLHI is indicated in patients with clinical deterioration associated with a significant mass effect, as observed on neuroimaging. However, with a reliable indicator of MLHI, early decompressive craniectomy before clinical deterioration may further reduce mortality and lead to a better functional outcome.

A Novel Long Non-Coding RNA-01488 Suppressed Metastasis and Tumorigenesis by Inducing miRNAs That Reduce Vimentin Expression and Ubiquitination of Cyclin E.

Long intergenic non-coding RNAs (lincRNAs) play important roles in human cancer development, including cell differentiation, apoptosis, and tumor progression. However, their underlying mechanisms of action are largely unknown at present. In this study, we focused on a novel suppressor lincRNA that has the potential to inhibit progression of human hepatocellular carcinoma (HCC). Our experiments disclosed long intergenic non-protein coding RNA 1488 (LINC01488) as a key negative regulator of HCC. Clinically, patients with high LINC01488 expression displayed greater survival rates and better prognosis. In vitro and in vivo functional assays showed that LINC01488 overexpression leads to significant suppression of cell proliferation and metastasis in HCC. Furthermore, LINC01488 bound to cyclin E to induce its ubiquitination and reduced expression of vimentin mediated by both miR-124-3p/miR-138-5p. Our results collectively indicate that LINC01488 acts as a tumor suppressor that inhibits metastasis and tumorigenesis in HCC via the miR-124-3p/miR-138-5p/vimentin axis. Furthermore, LINC01488 interacts with and degrades cyclin E, which contributes to its anti-tumorigenic activity. In view of these findings, we propose that enhancement of LINC01488 expression could be effective as a potential therapeutic strategy for HCC.

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Long non-coding (lnc) RNAs regulate complex cellular functions, such as cell growth, differentiation, metabolism, and metastasis. Although deregulation of lncRNA expression has been detected in HCC, many of the hepato-carcinogenesis-associated lncRNAs remain yet unidentified. Here, we aimed to investigate the involvement of a specific HCC-dysregulated lncRNA, FAM215A, and characterize its molecular regulation mechanism. We show for the first time that FAM215A is overexpressed in HCC, and its expression level correlates with tumor size, vascular invasion, and pathology stage. Overexpression of FAM215A accelerates cell proliferation and metastasis in HCC cells. According to Gene Expression Omnibus Dataset analysis, FAM215A is induced in doxorubicin (DOX)-resistant HCC cells. Overexpression of FAM215A increases DOX resistance in two HCC cell lines, and this is associated with enhanced expression of lysosome-associated membrane protein 2 (LAMP2). FAM215A interacts with LAMP2 to protect it from ubiquitination. Together, our results show that the lncRNA, FAM215A, is highly expressed in HCC, where it interacts with and stabilizes LAMP2 to increase tumor progression while decreasing doxorubicin sensitivity.