Long noncoding RNA MALAT1 inhibition attenuates sepsis-induced acute lung injury through modulating the miR-129-5p/PAX6/ZEB2 axis.

This research aimed to investigate the role of the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-129-5p (miR-129-5p)/paired box gene 6 (PAX6) axis in sepsis-induced acute lung injury (ALI). MLE-12 cells and C57BL/6 mice were induced by LPS to establish lung injury in in vitro and in vivo models. Cell viability and apoptosis were measured by cell counting kit-8 assay and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Levels of inflammatory cytokines in cell supernatants and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Lung injury was evaluated by lung wet weight-to-dry weight ratio and hematoxylin-eosin staining. MALAT1, PAX6, and zinc finger E-box-binding homeobox 2 (ZEB2) expression was elevated and miR-129-5p expression was reduced in the serum of patients with sepsis-induced ALI, LPS-induced MLE-12 cells, and lung tissues of ALI mice. MALAT1 interference delayed the LPS-induced cell proliferation decrease, apoptosis increase, and inflammatory factor increase. miR-129-5p inhibition could reverse the delaying effect of MALAT1 interference on LPS-induced lung cell injury. PAX6 overexpression (oe) reversed the inhibitory effect of miR-129-5p oe on LPS-induced lung cell injury. Downregulating MALAT1 reduced pulmonary edema, inflammatory cytokine levels, lung injury, and apoptosis in ALI mice. Moreover, miR-129-5p suppression or PAX6 oe reversed the delaying effect of MALAT1 interference on sepsis-induced ALI. MALAT1 aggravates sepsis-induced ALI via the miR-129-5p/PAX6/ZEB2 axis.

Role and Mechanism of lncRNA-pvt1 in the Pathogenesis of Acute Lymphoblastic Leukemia in Children.

Objective: To investigate the role and mechanism of lncRNA-pvt1 in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). Methods: The expression of lncRNA-pvt1 in bone marrow tissues of ALL patients after initial diagnosis and complete remission was detected by RT-PCR to explore its possible involvement in the pathogenesis of ALL. The proliferation and apoptosis of Jurkat cells transfected with lncRNA-pvt1 were observed by MTT and flow cytometry. Results: lncRNA-pvt1 expression was upregulated in bone marrow of ALL patients. Knockdown of lncRNA-pvt1 inhibited Jurkat cell proliferation and increased its apoptosis rate. Conclusion: Silencing lncRNA-pvt1 expression can inhibit the development of ALL.

Long Noncoding RNA LOC554202 Predicts a Poor Prognosis and Correlates with Immune Infiltration in Thyroid Cancer.

Thyroid cancer (TC) is one of the widely diagnosed carcinomas in women before the age of 30. Nevertheless, there is currently a lack of specific biomarkers for predicting the prognosis of TC. Long noncoding RNAs (lncRNAs) were important regulators in human cancer progression as previously described. Unfortunately, there is little known on these lncRNAs' functions and molecular mechanisms in TC. In our literature, we found that LOC554202 (MIR31HG) was upregulated in TC samples and correlated with clinicopathological features, including M stage, N stage, and lymph nodes examined status in TC. In addition, we found that LOC554202 overexpression was evidently correlated with high immune infiltrate levels of CD8+ T cells, macrophage, neutrophil, myeloid dendritic cells, and B cells in TC. Knockdown of LOC554202 impeded TC cell proliferation and cycle progression. We found that LOC554202 had an association with metabolic pathways, vesicle-mediated transport, tricarboxylic acid cycle, Hedgehog signaling pathway, and Hippo signaling pathway in TC. Reducing LOC554202 hindered TC cell proliferation and cycle progression. Finally, we found that LOC554202 participated in modulating the expression of the regulators of Hippo signaling and TCA pathway, such as CCND2, CCND3, SDHC, SDHD, SUCLA2, and SUCLG1. We thought that this study would largely enhance our understanding of LOC554202's functional roles in human TC progression and immune response.

Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin's Lymphoma.

The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin's lymphoma (NHL). By pyrosequencing-verified methylation-specific PCR, NKILA methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. NKILA methylation correlated with the repression of NKILA in cell lines. Hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and the re-expression of NKILA. In 102 NHL primary samples, NKILA was methylated in 29 (51.79%) diffuse large B-cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma cases, but unmethylated in all 26 mantle cell lymphoma cases. Mechanistically, the knockdown of NKILA resulted in promoting IkBα phosphorylation, associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-κB activation. Functionally, the knockdown of NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation. Collectively, NKILA was a tumor suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing resulted in increased cellular proliferation and decreased cell death via the repression of NF-κB signaling in NHL.

Overexpression of ultraconserved region 83- induces lung cancer tumorigenesis.

The expression of non-coding RNAs (ncRNAs) is dysregulated in human cancers. The transcribed ultraconserved regions (T-UCRs) express long ncRNAs involved in human carcinogenesis. T-UCRs are non-coding genomic sequence that are 100% conserved across humans, rats and mice. Conservation of genomic sequences across species intrinsically implies an essential functional role and so we considered the expression of T-UCRs in lung cancer. Using a custom microarray we analyzed the global expression of T-UCRs. Among these T-UCRs, the greatest variation was observed for antisense ultraconserved element 83 (uc.83-), which was upregulated in human lung cancer tissues compared with adjacent non cancerous tissues. Even though uc.83- is located within the long intergenic non-protein coding RNA 1876 (LINC01876) gene, we found that the transcribed uc.83- is expressed independently of LINC01876 and was cloned as a 1143-bp RNA gene. In this study, functional analysis confirmed important effects of uc.83- on genes involved in cell growth of human cells. siRNA against uc.83- decreased the growth of lung cancer cells while the upregulation through a vector overexpressing the uc.83- RNA increased cell proliferation. We also show the oncogenic function of uc.83- is mediated by the phosphorylation of AKT and ERK 1/2, two important biomarkers of lung cancer cell proliferation. Based on our findings, inhibition against uc.83- could be a future therapeutic treatment for NSCLC to achieve simultaneous blockade of pathways involved in lung carcinogenesis.

lncRNA H19 Aggravates Brain Injury in Rats following Experimental Intracerebral Hemorrhage via NF-κB Pathway.

OBJECTIVE: To explore the effect of long noncoding RNA H19 (lncRNA H19) on brain injury in rats following experimental intracerebral hemorrhage (ICH). METHODS: Rat ICH model was established with type IV collagenase. The neurological function scores were evaluated, and the water content in brain tissue was measured. The nerve injury indexes, inflammatory factors, and oxidative stress indexes were also measured. Moreover, the expression of lncRNA H19 was determined by qRT-PCR, and Western blot detected NF-κB pathway-related protein expression. RESULTS: Compared with the sham group, the neurological function scores, the water content in brain tissue, and levels of injury indicators myelin basic protein (MBP), S-100B, and neuron-specific enolase (NSE) in the ICH rats were significantly increased. Meanwhile, the levels of TNF-α, IL-6, IL-1ß, ROS, and MDA were significantly increased, but the levels of SOD were significantly decreased. In addition, the expression of lncRNA H19 in the brain tissue in the ICH group was significantly higher than that in the sham group. After further interference with lncRNA H19 expression (sh-H19 group), the levels of all the above indicators were reversed and the neurological damage was improved. Western blot results showed that the expression of NF-κBp65 and IKKß was significantly higher, and IκBα expression was lower in the perivascular hematoma tissue in the ICH group compared with the sham group. Compared with the sh-NC group, NF-κBp65 and IKKß expression were significantly lower and IκBα was significantly higher in the sh-H19 group. CONCLUSION: lncRNA H19 exacerbated brain injury in rats with ICH by promoting neurological impairment, brain edema, and releasing inflammatory responses and oxidative stress. This may be related to the activation of NF-κB signaling pathway.

LINC00511 Knockdown Suppresses Resistance to Cisplatin in Lung Adenocarcinoma by Interacting with miR-182-3p and BIRC5.

We studied the role of long intergenic non-protein coding RNA 00,511 (LINC00511) in lung adenocarcinoma (LUAD), with a specific focus on acquired chemoresistance. LINC00511 expression was higher in responders to cisplatin (DDP, another name for cisplantin) than non-responders, in A549/DDP cells than in parental A549 cells and normal human bronchial epithelial cells (16HBE). LINC00511 knockdown decreased the half maximal inhibitory concentration (IC50) value, suppressed A549/DDP cell viability, but induced apoptosis. LINC00511 bound with miR-182 and increased the expression of baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5). BIRC5 knockdown mimicked the effects of LINC00511 knockdown on the IC50 value, A549/DDP cell viability, and apoptosis. BIRC5 overexpression negated the effects of LINC00511 knockdown on A549/DDP cells. In vivo, LINC00511 knockdown attenuated the tumorigenesis of A549/DDP cells after DDP injection. These results provide a novel LINC00511/miR-182/BIRC5 paradigm to explain the mechanism of acquired DDP resistance.

Long non-coding RNA XIST alleviates sepsis-induced acute kidney injury through inhibiting inflammation and cell apoptosis via regulating miR-155-5p/WWC1 axis.

Sepsis is characterized by a severe inflammatory response throughout the whole body and can induce acute kidney injury (AKI). This research aimed to investigate the regulatory mechanisms underlying miR-155-5p in sepsis-induced AKI. CLP-treated mice were used as an in vivo model of sepsis-induced AKI, and LPS-treated HK-2 and TCMK-1 cells were used as in vitro models. Bioinformatics analyses and mechanistic assays were utilized to reveal the relationships between molecules. H&E staining was used to reveal morphological changes in kidney tissues. ELISAs were conducted to detect the concentrations of proinflammatory cytokines. We discovered that miR-155-5p was prominently upregulated in sepsis-induced AKI in vivo and in vitro. MiR-155-5p inhibition alleviated kidney injury in mice. Moreover, WWC1 served as a direct target of miR-155-5p and was negatively regulated by miR-155-5p. WWC1 upregulation inhibited the productions of inflammatory cytokines and suppressed apoptosis in vivo and in vitro. In addition, rescue assays demonstrated that WWC1 knockdown counteracted the inhibitory effect of anti-miR-155-5p on inflammation and apoptosis. Moreover, miR-155-5p could bind to XIST. XIST expression was downregulated in LPS-stimulated HK-2 and TCMK-1 cells. XIST could negatively regulate miR-155-5p expression and positively regulate WWC1 expression. Rescue assays revealed that miR-155-5p overexpression significantly reversed the suppressive effects of XIST upregulation on inflammation and apoptosis. In conclusion, our study revealed that the XIST/miR-155-5p/WWC1 axis modulated sepsis-induced AKI progression, providing promising insight into therapeutic targets for sepsis-induced AKI.

Hindering the Synchronization Between miR-486-5p and H19 lncRNA by Hesperetin Halts Breast Cancer Aggressiveness Through Tuning ICAM-1.

BACKGROUND: Recently, a novel crosstalk between non-coding RNAs (ncRNAs) has been casted. However, this has been seldom investigated in metastatic BC (mBC). H19 and miR-486-5p role in mBC are controversial. ICAM-1 is a recently recognized metastatic engine in mBC. Natural compounds were recently found to alter ncRNAs/target circuits. Yet, Hesperitin's modulatory role in altering such circuits has never been investigated in mBC. OBJECTIVE: The aim of this study is to investigate the impact of hesperitin on miR-486-5p/H19/ICAM-1 axis. METHODS: BC patients (n=20) were recruited in the study. Bioinformatic analysis was performed using different prediction softwares. MDA-MB-231 and MCF-7 cells were cultured and transfected using several oligonucleotides or treated with serial dilutions of hesperitin. RNA was extracted and gene expression analysis was performed using q-RT-PCR. ICAM-1 protein levels were assessed using human ICAM-1 Elisa Kit. Cytotoxic potential of hesperitin against normal cells was assessed by LDH assay. Several functional analysis experiments were performed such as MTT, colony forming and migration assays. RESULTS: The study showed that miR-486-5p and H19 had paradoxical expression profiles in BC patients. miR- 486-5p mimics and H19 siRNAs repressed ICAM-1 and halted mBC hallmarks. A novel crosstalk between miR- 486-5p and H19 was observed highlighting a bi-directional relationship between them. Hesperetin restored the expression of miR-486-5p, inhibited H19 lncRNA and ICAM-1 expression and selectively regressed mBC cell aggressiveness. CONCLUSION: miR-486-5p and H19 are inter-connected upstream regulators for ICAM-1 building up miR-486- 5p/H19/ICAM-1 axis that has been successfully tuned in mBC cells by hesperitin.

The long noncoding RNA GAS5 potentiates neuronal injury in Parkinson's disease by binding to microRNA-150 to regulate Fosl1 expression.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been the focus of recent studies of neurodegenerative disorders, including Parkinson's disease (PD). However, the specific mechanism of action of growth arrest-specific 5 (GAS5) in PD has not yet been characterized. First, the GSE8030 and GSE16658 datasets were analyzed to obtain differentially expressed genes (DEGs), followed by the development of a PD mouse model. The effects of shRNA targeting fos-like antigen-1 (shFosl1) and microRNA (miR)-150 agomiR on PD mouse behavior and neuronal injury were evaluated in vitro and in vivo. After the determination of target lncRNAs using bioinformatics tools, cell models were developed in SH-SY5Y and N2a cells using MPP+ to verify the effects of GAS5, miR-150 and Fosl1 on cell viability. Knockdown of Fosl1 and GAS5 or overexpression of miR-150 alleviated neuronal injury in mice after MPTP treatment and significantly increased the activity of SH-SY5Y and N2a cells after MPP treatment. GAS5 bound to miR-150, while miR-150 targeted Fosl1. Fosl1 activated the PTEN/AKT/mTOR pathway, thus promoting apoptosis and inhibiting neuronal activity in the PD model. Overall, our findings illuminated that GAS5 accelerated PD progression by targeting the miR-150/Fosl1 axis.

Inhibition of lncRNA NEAT1 protects endothelial cells against hypoxia/reoxygenation­induced NLRP3 inflammasome activation by targeting the miR­204/BRCC3 axis.

Cardiovascular ischemia/reperfusion (I/R) injury is primarily caused by oxygen recovery after prolonged hypoxia. Previous studies found that the long non coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was involved in cardiovascular pathology, and that NOD­like receptor protein 3 (NLRP3) inflammasome activation­dependent pyroptosis played a key role in cardiovascular I/R injury. The present study aimed to explore the molecular mechanism of I/R pathogenesis in order to provide novel insights for potential future therapies. Cell viability and lactate dehydrogenase enzyme activity assays were used to detect cell injury after human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia/reoxygenation (H/R). The expression of the NEAT1/microRNA (miR)­204/BRCA1/BRCA2­containing complex subunit 3 (BRCC3) axis was examined by reverse transcription­quantitative PCR, and the associations among genes were confirmed by luciferase reporter assays. Western blotting and ELISA were used to measure the level of NLRP3 inflammasome activation­dependent pyroptosis. The results demonstrated that NEAT1, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis were significantly increased in H/R­injured HUVECs, whereas silencing BRCC3 or NEAT1 attenuated H/R­induced injury and pyroptosis. NEAT1 positively regulated BRCC3 expression via competitively binding with miR­204. Moreover, NEAT1 overexpression counteracted miR­204 mimic­induced injury, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis. Taken together, these findings demonstrated that inhibition of lncRNA NEAT1 protects HUVECs against H/R­induced NLRP3 inflammasome activation by targeting the miR­204/BRCC3 axis.

Knockdown of lncRNA FOXD2-AS1 Inhibits Proliferation, Migration, and Drug Resistance of Breast Cancer Cells.

OBJECTIVE: In order to investigate the effect of lncRNA FOXD2-AS1 on breast cancer cells proliferation, migration, and drug resistance as well as its molecular mechanism. METHODS: Real-time PCR was used to detect the expression of breast cancer tissues and cells from patients admitted to our hospital and the expression of lncRNA FOXD2-AS1 in MCF-7/ADR in adriamycin- (ADR-) resistant breast cancer cells. After interfering with or overexpressing lncRNA FOXD2-AS1 in MCF-7/ADR cells, cell proliferation, apoptosis, invasion, and migration were detected using CCK-8, flow cytometry, Transwell assay, and scratch test, respectively. The protein levels of PI3K, p-PI3K, AKT, and p-AKT in the PI3K/AKT signaling pathway were detected by Western blot. RESULTS: lncRNA FOXD2-AS1 was upregulated in breast cancer tissues and cells and increased cell drug resistance to ADR. Downregulation of lncRNA FOXD2-AS1 inhibited invasion and migration of MCF-7/ADR cells, promoted apoptosis, increased chemosensitivity of MCF-7/ADR cells, and inhibited the activity of PI3K/AKT signaling pathway in MCF-7/ADR cells. CONCLUSIONS: lncRNA FOXD2-AS1 can promote the proliferation, invasion, migration, and drug resistance of breast cancer cells, inhibit apoptosis, and accelerate the development of breast cancer by positively regulating the PI3K/AKT signaling pathway.

LncRNA PVT1 Promotes Hypoxia-Induced Cardiomyocyte Injury by Inhibiting miR-214-3p.

OBJECTIVE: To explore the effect and related mechanism of LncRNA PVT1 on hypoxia-induced cardiomyocyte injury. METHODS: PVT1RNA and miR-214-3p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell vitality and apoptosis were, respectively, evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis. Starbase and Dual luciferase reporter (DLR) gene assay was employed to validate the interaction between miR-214-3p and PVT1. RESULTS: PVT1 was statistically upregulated, and miR-214-3p was statistically downregulated in hypoxia-induced H9c2 cells. The survival rate of H9c2 cells induced by hypoxia decreased statistically, while the apoptosis rate increased statistically (P < 0.05). PVT1 knockdown upregulated the hypoxia-induced H9c2 cell viability and inhibited apoptosis. DLR assay verified the targeting relationship between PVT1 and miR-214-3p. In addition, miR-214-3p inhibitors reversed the viability of H9c2 cells with PVT1 knockout and promoted apoptosis. CONCLUSION: Silencing PVT1 can enhance the hypoxia-induced H9c2 cell viability and inhibit apoptosis, providing a potential target for the treatment of cardiovascular diseases.

Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression.

BACKGROUND: Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. METHODS: Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. RESULTS: We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. CONCLUSIONS: The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

LncRNA HOXA11-AS aggravates the keloid formation by targeting miR-148b-3p/IGFBP5 axis.

Long non-coding RNA (lncRNA) homeobox (HOX) A11 antisense (HOXA11-AS) mediates cell-biological phenotypes of keloid fibroblasts and influence the keloid progression, yet the underlying mechanism need to be further understood. HOXA11-AS, microRNA miR-148b-3p and Insulin like growth factor binding protein 5 (IGFBP5) expression were detected by RT-qPCR or western blot. CCK-8 and colony formation assays were applied to examine the cell proliferation. The cell migration was determined via Transwell migration assays. The cell apoptosis was determined by western blots with anti-Bax antibodies and anti-Cleaved Caspase-3 antibodies. The interplay between miR-148b-3p, HOXA11-AS and IGFBP5 was confirmed by luciferase reporter or RNA immunoprecipitation assay. The amplification of HOXA11-AS and IGFBP5 was detected in keloid and keloid fibroblasts, while miR-148b-3p expression was reduced. Moreover, downregulation of HOXA11-AS in keloid fibroblasts inhibited cell proliferation, migration and triggered apoptosis. Mechanically, HOXA11-AS was proved to sponge miR-148b-3p and abrogate the inhibition on miR-148b-3p target, IGFBP5 mRNA, thus promoting keloid fibroblasts proliferation, migration and inhibiting apoptosis. These results find that HOXA11-AS promotes keloid progression by miR-148b-3p/IGFBP5 axis, suggesting the potential of targeting HOXA11-AS/miR-148b-3p/IGFBP5 axis to combat keloid.

USP30-AS1 contributes to mitochondrial quality control in glioblastoma cells.

Glioblastoma is the most serious type of brain cancer with poor prognosis. Here, using the publicly available glioma database, we identified that USP30-AS1, an antisense lncRNA locating on the opposite strand of USP30 locus, is upregulated in human gliomas, particularly in high grade glioma. High level of USP30-AS1 is correlated with poor survival in both primary and recurrent glioma patients. USP30-AS1 regulates mitochondrial homeostasis and mitophagy in glioblastoma cells. Knockdown of USP30-AS1 decreases mitochondrial protein expression and mitochondrial mass, promotes mitochondrial uncoupler-induced mitophagy. However, USP30-AS1 does not regulate USP30 expression in a cis-regulatory manner. In summary, this study proposed that USP30-AS1 may serve as a valuable prognostic marker for gliomas. USP3-AS1 is a negative regulator of mitophagy and the regulatory effect is USP30-independent. USP30-AS1 mediated repression of mitophagy may contribute to the loss of mitochondrial homeostasis and tumor development in glioma.

Long non-coding RNA BACE1-AS plays an oncogenic role in hepatocellular carcinoma cells through miR-214-3p/APLN axis.

BACE1 antisense RNA (BACE1-AS) is implicated in promoting cell proliferation in different types of tumors. However, the function and mechanism of BACE1-AS in hepatocellular carcinoma (HCC) are still unclear. In the present study, we found that the relative expression of BACE1-AS in HCC cell lines, HCC tissues, and serum samples of HCC patients was significantly increased, and its high expression was correlated with the poor prognosis of HCC patients. In addition, overexpression of BACE1 promoted HCC cell proliferation, cell cycle progression, migration, and invasion, but inhibited cell apoptosis, while knockdown of BACE1 exerted the opposite role. Furthermore, BACE1-AS sponged miR-214-3p and inhibited its expression, thus promoting Apelin (APLN) expression. Overexpression or knockdown of miR-214-3p could partially reverse the abnormal proliferation, cell cycle progression, migration, invasion, and apoptosis caused by overexpression or knockdown of BACE1. These findings suggest that the BACE1-AS/miR-214-3p/APLN axis is a novel signaling pathway that facilitates HCC.

Silencing long noncoding RNA LINC01138 inhibits aerobic glycolysis to reduce glioma cell proliferation by regulating the microRNA­375/SP1 axis.

Glioma is a primary cerebral neoplasm that originates from glial tissue and spreads to the central nervous system. Long noncoding RNAs are known to play a role in glioma cells by regulating cell proliferation, migration and invasion. The aim of the present study was to investigate the mechanism by which long intergenic non­protein coding RNA (LINC) 01138 affects glycolysis and proliferation in glioma cells via the microRNA (miR)­375/specificity protein 1 (SP1) axis. LINC01138 expression was assessed in glioma tissues and cells using reverse transcription­quantitative PCR and the association between LINC01138 and patient clinicopathological features was analyzed. Glucose uptake, lactic acid secretion, cell proliferation, and glycolysis­related enzyme levels were detected following LINC01138 silencing using CCK­8, EDU assay and western blot analysis. miR­375 and SP1 expression levels were also assessed, and the distribution of LINC01138 in the nucleus and cytoplasm was investigated using subcellular fractionation localization. Furthermore, the binding relationships between LINC01138 and miR­375, and between miR­375 and SP1 were assessed via dual­luciferase experiment, RIP and RNA pull­down assays. Finally, xenograft transplantation models were used to verify the in vitro results. LINC01138 was highly expressed in glioma, which was independent of patient sex or age but was significantly related to tumor diameter, the World Health Organization tumor grade and lymph node metastasis. Silencing LINC01138 significantly reduced glioma glycolysis and cell proliferation. Moreover, LINC01138 acted as a competing endogenous RNA to sponge miR­375 and promote SP1 expression. miR­375 inhibition significantly reversed the effect of LINC01138 silencing. In addition, silencing LINC01138 significantly reduced tumor growth in vivo. The present study demonstrated that silencing LINC01138 inhibited aerobic glycolysis and thus reduced glioma cell proliferation, potentially by modulating the miR­375/SP1 axis.

Noncoding RNAs in triple negative breast cancer: Mechanisms for chemoresistance.

Triple-negative breast cancer (TNBC) is the most aggressive subtype among breast cancers with high recurrence and this condition is partly due to chemoresistance. Therefore, fully understanding the mechanism of TNBC-resistance is the key to overcoming chemoresistance, which will be an effective strategy for TNBC therapy. Various potential mechanisms involved in the chemoresistance of TNBC have been investigated and indicated that noncoding RNAs (ncRNAs) especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) take part in most TNBC resistance. The ncRNA-induced chemoresistance process is involved in the alteration of many activities. here, we mainly summarize the mechanisms of ncRNAs in the chemoresistance of TNBC and discuss the potential clinical application of ncRNAs in the treatment of TNBC, indicating that targeting ncRNAs might be a promising strategy for resensitization to chemotherapies.