Intergenic Non-protein Coding RNA Research Articles

Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis.

The role of microglia in traumatic brain injury (TBI) has gained considerable attention. The present study aims to elucidate the potential mechanisms of Long intergenic non-protein coding RNA 707 (LINC00707) in TBI-induced microglia activation and inflammatory factor release. An in vivo model of rat TBI and in vitro microglia model was established using Controlled cortex injury (CCI) and lipopolysaccharide (LPS) stimulation. RT-qPCR to detect LINC00707 levels in rat cerebral cortex or cells. Modified Neurological Impairment Score (mNSS) and Morris Water Maze test was conducted to assess the neurological deficits and cognitive impairment. ELISA analysis of pro-inflammatory factors levels. CCK-8 and flow cytometry for cell viability and apoptosis levels. Dual-luciferase report and RIP assay to validate the targeting relationship between LINC00707 and miR-30a-5p. LINC00707 was elevated in the TBI rat cerebral cortex and LPS-induced microglia, while miR-30a-5p was noticeably decreased (P < 0.05). Increased mNSS, cognitive dysfunction, and brain edema in TBI rats were all prominently reversed by silencing of LINC00707, but this reversal was partially abrogated by decreasing miR-30a-5p (P < 0.05). Inhibition of LINC00707 suppressed the overproduction of inflammatory factors in TBI rats (P < 0.05). LPS decreased microglial cell viability, increased apoptosis, and promoted inflammatory overproduction than control, but the silencing of LINC00707 reversed its effect. Suppression of miR-30a-5p attenuated this reversal (P < 0.05). miR-30a-5p was the target miRNA of LINC00707.All in all, the results suggested that inhibiting LINC00707/miR-30a-5p axis could alleviate the progression of TBI by suppressing the inflammation and apoptosis of microglia cells.

LINC-PINT suppresses breast cancer cell proliferation and migration via MEIS2/PPP3CC/NF-κB pathway by sponging miR-576-5p

BackgroundBreast cancer (BCa) is the most frequent malignant tumor in women. Long non-coding RNAs (lncRNAs) have been acknowledged to exert critical regulating functions in various cancers. Long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT) has been reported to be a chemosensitizer and a tumor suppressor in BCa. However, its downstream molecular mechanism contributing to its tumor-suppressing role remains to be explored in BCa. MethodsLINC-PINT expression in BCa tissues and cells was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The proliferation of transfected BCa cells was examined by counting kit-8 (CCK-8) and EdU assay. The migrating ability of indicate BCa cells was assessed by wound healing assays. Bioinformatics analysis and mechanism experiments such as RNA immunoprecipitation (RIP), RNA pull down assay, and luciferase reporter assay, were applied to demonstrate the downstream targets of LINC-PINT. ResultsLINC-PINT was downregulated in BCa tissues and cell lines. Overexpression of LINC-PINT suppressed BCa cell proliferation and migration. LINC-PINT could interact with miR-576-5p to upregulate Meis homeobox 2 (MEIS2) that positively regulated protein phosphatase 3 catalytic subunit gamma (PPP3CC) by inactivating the nuclear factor-κB (NF-κB) pathway. ConclusionsThese findings elucidated the anti-tumor role of LINC-PINT in BCa via the miR-576-5p/MEIS2/PPP3CC/NF-κB axis, which suggested that LINC-PINT might serve as a potential therapeutic target for BCa.

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

The expression of lncRNAs CASC2, NEAT1, LINC00299 in breast cancer tissues and their relationship with the XBP1 splicing rate in Iranian patients during 2014-2019: A cross-sectional study.

Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway. Total RNA was extracted from 40 samples of breast tumor tissues and their respective controls. The expression level of lncRNAs CASC2, NEAT1, and LINC00299 was quantified using reverse transcription-polymerase chain reaction (RT-PCR). The ratio of the spliced form of XBP1 to its unspliced form (XBP1u) was determined by PCR and electrophoresis. The results showed a 2.8-fold increase in the ratio of XBP1s/u in breast cancer tissues compared to adjacent nonmalignant samples (p < 0.05). Additionally, the level of lncRNAs NEAT1, CASC2, and LINC00299 in breast tumor tissues increased significantly by twofold, 1.5-fold, and 2.3-fold, respectively, compared to adjacent nonmalignant samples (p < 0.05). Based on the association between the expression of lncRNAs CASC2, LINC00299, and NEAT1 and the XBP1s/u ratio, these lncRNAs could be potential regulators of the UPR pathway. Also, CASC2 and NEAT1 genes could be suggested as suitable biomarkers to distinguish cancerous tissue from noncancerous breast tissue due to their significant increase in expression in cancerous samples compared to adjacent noncancerous.

Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma

ObjectiveTo screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed.MethodsFirst, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed.ResultsSeven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p—EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression.ConclusionThis study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p—EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.

Long intergenic non-protein-coding RNA 1547 acts as a competing endogenous RNA and exerts cancer-promoting activity in non-small cell lung cancer by targeting the microRNA-195-5p/ homeobox C8 axis

Long intergenic non-protein coding RNA 1547 (LINC01547) presents a notable relationship with prognosis in patients with ovarian cancer. Herein, we examined the expression of LINC01547 in non-small cell lung cancer (NSCLC) to ascertain its clinical significance. We also explored the detailed functions of LINC01547 in regulating the aggressive phenotype of NSCLC and the molecular mechanism of action underlying its carcinogenic activities events in NSCLC. Furthermore, we applied the data acquired from the tissue specimens and the Cancer Genome Atlas (TCGA) database to analyze the level of LINC01547 in NSCLC and conducted functional assays to address the regulatory effect of LINC01547. Further, we examined the mechanistic interaction among LINC01547, microRNA-195-5p (miR-195-5p), and homeobox C8 (HOXC8) using bioinformatics prediction and luciferase reporter assay. LINC01547 was noticeably overexpressed, as affirmed by data from TCGA and our own cohort; moreover, poor prognosis was associated with increased LINC01547 levels in patients with NSCLC. LINC01547 regulates cell proliferation, colony-forming, migration, and invasion, and its absence produced tumor-repressing effects in NSCLC. Mechanistically, as a competitive endogenous RNA, LINC01547 decoyed miR-195-5p and consequently resulted in the overexpression of HOXC8 in NSCLC cells. Using rescue experiments, we found that the regulatory activities of LINC01547 deficient in repressing the malignant properties of NSCLC cells could be counteracted by hindering miR-195-5p or overexpressing HOXC8. Conclusively, LINC01547 serves as a crucial component to worsen the oncogenicity of NSCLC cells by controlling the miR-195-5p/HOXC8 axis. Thus, the newly identified competing endogenous RNA pathway may potentially be an attractive therapeutic for NSCLC management.

Long Intergenic Non-Protein Coding RNA 519 Promotes the Biological Activities of Tongue Squamous Cell Carcinoma by Sponging microRNA-876-3p and Consequently Upregulating MACC1 [Retraction

[This retracts the article DOI: 10.2147/OTT.S279798.].

LINC00641 impeded the malignant biological behaviors of papillary thyroid carcinoma cells via interacting with IGF2BP1 to reduce GLI1 mRNA stability.

Dysregulation of long intergenic non-protein coding RNA 00,641 (LINC00641) is associated with the malignancy progression of multiple cancers, including thyroid carcinoma. The current study aimed to determine the role of LINC00641 in papillary thyroid carcinoma (PTC) and the underlying mechanism. We found that LINC00641 was downregulated in PTC tissues and cells(p < 0.05), and overexpression of LINC00641 inhibited PTC cell proliferation and invasion, and induced apoptosis(p < 0.05), while silencing LINC00641 promoted the proliferation and invasion in PTC cells, and inhibited cell apoptosis(p < 0.05). Furthermore, we found that Glioma-associated oncogene homolog 1 (GLI1) expression was negatively correlated with LINC00641 expression in PTC tissues (r2 = 0.7649, p < 0.0001), and silencing GLI1 inhibited PTC cell proliferation and invasion, and induced apoptosis(p < 0.05). Meanwhile, RNA immunoprecipitation (RIP) and RNA pull-down assays confirmed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) bound to LINC00641 as an RNA binding protein, and overexpression of LINC00641 destabilized GLI1 mRNA by competitively binding to IGF2BP1. Rescue experiments revealed that overexpression of GLI1 restored the inhibitory effect of LINC00641 overexpression on activation of the AKT pathway, as well as PTC cell proliferation and invasion, and counteracted the induction of cell apoptosis by LINC00641 overexpression. Finally, in vivo experimental results showed that overexpression of LINC00641 markedly suppressed tumor growth and reduced expression of GLI1 and p-AKT in xenograft tumor mice(p < 0.05). In summary, this study highlighted that LINC00641 plays a critical role in the malignant biological progression of PTC by regulating the LINC00641/IGF2BP1/GLI1/AKT signaling pathway, which may serve as a potential therapeutic target for PTC.

Correction for: Long intergenic non-protein coding RNA 324 prevents breast cancer progression by modulating miR-10b-5p.

Correction for: Long intergenic non-protein coding RNA 324 prevents breast cancer progression by modulating miR-10b-5p.

LINC01060 knockdown inhibits osteosarcoma cell malignant behaviors in vitro and tumor growth and metastasis in vivo through the PI3K/Akt signaling

ABSTRACT Despite its low frequency, osteosarcoma is one of the deadliest malignancies in children and adolescents. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling activation and epithelial-to-mesenchymal transition (EMT) are critical issues during osteosarcoma development. This study found long intergenic non-protein coding RNA 1060 (LINC01060) to be an EMT-related long non-coding RNA (lncRNA) up-regulated in osteosarcoma; higher LINC01060 expression was linked to a worse prognosis in osteosarcoma patients. In vitro, knocking down LINC01060 significantly inhibits osteosarcoma cell malignant behaviors, including hyperproliferation, invasion, migration, and EMT. In vivo, LINC01060 knockdown inhibited tumor growth and metastasis, and suppressed PI3K and Akt phosphorylation. In osteosarcoma cells, Akt agonist SC79 exerted opposite effects to those of LINC01060 knockdown through the promotion of cell viability, cell migration, and cell invasion. Moreover, the Akt agonist SC79 partially eliminated LINC01060 knockdown effects on osteosarcoma cells, suggesting that LINC01060 exerts its effects through the PI3K/Akt signaling. Therefore, it is deduced that LINC01060 is overexpressed in osteosarcoma. In vitro, LINC01060 knockdown inhibits cancer cell malignant behaviors; in vivo, LINC01060 knockdown inhibits tumor development and metastasis. The PI3K/Akt signaling is involved in LINC01060 functions in osteosarcoma.

LINC00659 Inhibits Hepatocellular Carcinoma Malignant Progression by Blocking Aerobic Glycolysis through FUS Recruitment and SLC10A1 Modulation.

Hepatocellular carcinoma (HCC) is a malignant type of liver cancer that poses severe threat to human health worldwide. Aerobic glycolysis is a hallmark of HCC and facilitates its progression. Solute carrier family 10 member 1 (SLC10A1) and long intergenic non-protein coding RNA 659 (LINC00659) were detected to be downregulated in HCC cells, yet their potential functions underlying HCC progression remained unidentified. In the current work, colony formation and transwell assays were used to detect HCC cells (HepG2 and HuH-7) proliferation and migration in vitro study. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used for gene/protein expression determination. Seahorse assay was performed for aerobic glycolysis assessment. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted for detection of the molecular interaction between LINC00659 and SLC10A1. The results showed that overexpressed SLC10A1 significantly suppressed the proliferation, migration, and aerobic glycolysis in HCC cells. Mechanical experiments further demonstrated that LINC00659 positively regulated SLC10A1 expression in HCC cells by recruiting fused protein in sarcoma (FUS). Our work elucidated that LINC00659 inhibited HCC progression and aerobic glycolysis via the FUS/SLC10A1 axis, revealing a novel lncRNA-RNA-binding protein-mRNA network in HCC, which might provide potential therapeutic targets for HCC.

Long Intergenic Non-Protein Coding RNA 00342 Exerts Oncogenic Effects in Prostate Cancer by Sponging microRNA-19b-3p and Thereby Increasing Forkhead Box F2 Expression

Prostate cancer is one of the most common malignancies in males with increasing morbidity and mortality. Related reports indicate that lncRNAs may be a new class of potential tumor molecular markers. Compared with the normal tissues, the expression level of LINC00342 in prostate cancer tissues was significantly increased. Compared with normal PC3 and DU145 cells, cells silenced by the LINC00342 gene significantly decreased the ability of proliferation, migration, invasion, and induced apoptosis. Further, the FISH assay showed that LINC00342 could interact with miR-19b-3p and control the expression of Forkhead Box F2 (FOXF2), the target of miR-19b-3p. LINC00342 could activate the ERK/AKT signaling pathways. Tumor xenograft formation assay demonstrated that the down-regulated LINC00342 prevented tumor formation in vivo. Taken together, these results indicated that the interference of LINC00342 expression might inhibit the invasion, migration and promote apoptosis of prostate cancer cells by inhibiting the ERK1/2/AKT signaling pathway via sponging miRNA-19b-3p and thereby increasing FOXF2 expression.

A review on the role of LINC00511 in cancer.

Long Intergenic Non-Protein Coding RNA 511 (LINC00511) is an RNA gene being mostly associated with lung cancer. Further assessments have shown dysregulation of this lncRNA in a variety of cancers. LINC00511 has interactions with hsa-miR-29b-3p, hsa-miR-765, hsa-mir-150, miR-1231, TFAP2A-AS2, hsa-miR-185-3p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, RAD51-AS1 and EZH2. A number of transcription factors have been identified that regulate expression of LINC00511. The current narrative review summarizes the role of LINC00511 in different cancers with an especial focus on its prognostic impact in human cancers.

Anoikis resistance of small airway epithelium is involved in the progression of chronic obstructive pulmonary disease.

Anoikis resistance is recognized as a crucial step in the metastasis of cancer cells. Most epithelial tumors are distinguished by the ability of epithelial cells to abscond anoikis when detached from the extracellular matrix. However, no study has investigated the involvement of anoikis in the small airway epithelium (SAE) of chronic obstructive pulmonary disease (COPD). Anoikis-related genes (ANRGs) exhibiting differential expression in COPD were identified using microarray datasets obtained from the Gene Expression Omnibus (GEO) database. Unsupervised clustering was performed to classify COPD patients into anoikis-related subtypes. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to annotate the functions between different subtypes. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were leveraged to identify key molecules. The relative proportion of infiltrating immune cells in the SAE was quantified using the CIBERSORT and ssGSEA computational algorithms, and the correlation between key molecules and immune cell abundance was analyzed. The expression of key molecules in BEAS-2B cells exposed to cigarette smoke extract (CSE) was validated using qRT-PCR. A total of 25 ANRGs exhibited differential expression in the SAE of COPD patients, based on which two subtypes of COPD patients with distinct anoikis patterns were identified. COPD patients with anoikis resistance had more advanced GOLD stages and cigarette consumption. Functional annotations revealed a different immune status between COPD patients with pro-anoikis and anoikis resistance. Tenomodulin (TNMD) and long intergenic non-protein coding RNA 656 (LINC00656) were subsequently identified as key molecules involved in this process, and a close correlation between TNMD and the infiltrating immune cells was observed, such as activated CD4+ memory T cells, M1 macrophages, and activated NK cells. Further enrichment analyses clarified the relationship between TNMD and the inflammatory and apoptotic signaling pathway as the potential mechanism for regulating anoikis. In vitro experiments showed a dramatic upregulation of TNMD and LINC00656 in BEAS-2B cells when exposed to 3% CSE for 48 hours. TNMD contributes to the progression of COPD by inducing anoikis resistance in SAE, which is intimately associated with the immune microenvironment.

Linc-ROR Promotes EMT by Targeting miR-204-5p/SMAD4 in Endometriosis.

Endometriosis (EMs) is a systemic and chronic disease with cancer-like feature, namely, distant implantation, which caused heavy healthy burden of nearly 200 million females. LncRNAs have been proved as new modulators in epithelial-mesenchymal transition (EMT) and EMs. Quantitative real-time PCR was conducted to measure the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR), and miR-204-5p in ectopic endometrium (n = 25), eutopic endometrium (n = 20), and natural control endometrium (n = 22). Overexpression of Linc-ROR, knockdown or overexpression of miR-204-5p in End1/E6E7 and Ishikawa cells, was conducted to detect the function of Linc-ROR and miR-204-5p in EMs. Furthermore, luciferase reports were used to confirm the combination of Linc-ROR and miR-204-5p and the combination between miR-204-5p and SMAD4. Cell-Counting Kit-8, EdU assay, transwell assays, and Western blotting were used to detect the function of Linc-ROR and miR-204-5p in EMs cancer-like behaviors and EMT process. Linc-ROR was up-regulated in ectopic endometrium. Overexpressed Linc-ROR promotes cell proliferation, invasion, and EMT process. Linc-ROR regulated the EMT process, cellular proliferation, and invasion of EMs via binding to miR-204-5p. In addition, overexpression of Linc-ROR up-regulated SMAD4, a target protein of miR-204-5p, with which regulated EMT process and cancer-like behaviors in EMs together. Linc-ROR/miR-204-5p/SMAD4 axis plays a vital role in regulation EMT process in EMs, which might become a novel therapeutic targets and powerful biomarkers in EMs therapy.

A review on the role of LINC00173 in human cancers.

Long intergenic non-protein coding RNA 173 (LINC00173) is a long non-coding RNA with especial function in the tumorigenic process. Studies in different types of cancers support an oncogenic role for LINC00173 except for studies in B-cell precursor acute lymphoblastic leukemia, cervical cancer, pancreatic cancer and gastric cancer. In breast and lung cancers, both oncogenic and tumor suppressor roles have been reported for LINC00173. LINC00173 can serve as a molecular sponge for miRNAs. miR-218/Etk, miR-511-5p/VEGFA, miR-182-5p/AGER, miR-765/NUTF2, miR-765/PLP2, miR-182-5p/FBXW7, miR-338-3p/Rab25, miR‑641/RAB14 and miR-1275/BCL2 are examples of the miRNA/mRNA axes being regulated by LINC00173 in the context of cancer. The current review provides a summary of different studies on the role of LINC00173 in these cancers.

Long intergenic non-protein coding RNA 00858 participates in the occurrence and development of esophageal squamous cell carcinoma through the activation of the FTO-m6A-MYC axis by recruiting ZNF184

ObjectivesWe aimed at probing impact of LINC00858 on esophageal squamous cell carcinoma (ESCC) progression via ZNF184-FTO-m6A-MYC axis. MethodsExpression of related genes (LINC00858, ZNF184, FTO, and MYC) was detected in ESCC tissues or cells and their relationships were assessed. After expression alterations in ESCC cells, cell proliferation, invasion, migration, and apoptosis were detected. Tumor formation in nude mice was conducted. ResultsLINC00858, ZNF184, FTO, and MYC were overexpressed in ESCC tissues and cells. LINC00858 enhanced ZNF184 expression to upregulate FTO, which augmented MYC expression. LINC00858 knockdown diminished ESCC cell proliferative, migratory, and invasive properties while elevating apoptosis, which was negated by FTO overexpression. FTO knockdown exerted similar functions of LINC00858 knockdown on ESCC cell movements, which was annulled by MYC upregulation. Silencing LINC00858 repressed tumor growth and related gene expression in nude mice. ConclusionsLINC00858 modulated MYC m6A modification via FTO by recruiting ZNF184, thus facilitating ESCC progression.

HERV-W ENV Induces Innate Immune Activation and Neuronal Apoptosis via linc01930/cGAS Axis in Recent-Onset Schizophrenia.

Schizophrenia is a severe neuropsychiatric disorder affecting about 1% of individuals worldwide. Increased innate immune activation and neuronal apoptosis are common findings in schizophrenia. Interferon beta (IFN-β), an essential cytokine in promoting and regulating innate immune responses, causes neuronal apoptosis in vitro. However, the precise pathogenesis of schizophrenia is unknown. Recent studies indicate that a domesticated endogenous retroviral envelope glycoprotein of the W family (HERV-W ENV, also called ERVWE1 or syncytin 1), derived from the endogenous retrovirus group W member 1 (ERVWE1) locus on chromosome 7q21.2, has a high level in schizophrenia. Here, we found an increased serum IFN-β level in schizophrenia and showed a positive correlation with HERV-W ENV. In addition, serum long intergenic non-protein coding RNA 1930 (linc01930), decreased in schizophrenia, was negatively correlated with HERV-W ENV and IFN-β. In vitro experiments showed that linc01930, mainly in the nucleus and with noncoding functions, was repressed by HERV-W ENV through promoter activity suppression. Further studies indicated that HERV-W ENV increased IFN-β expression and neuronal apoptosis by restraining the expression of linc01930. Furthermore, HERV-W ENV enhanced cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes protein (STING) expression and interferon regulatory factor 3 (IRF3) phosphorylation in neuronal cells. Notably, cGAS interacted with HERV-W ENV and triggered IFN-β expression and neuronal apoptosis caused by HERV-W ENV. Moreover, Linc01930 participated in the increased neuronal apoptosis and expression level of cGAS and IFN-β induced by HERV-W ENV. To summarize, our results suggested that linc01930 and IFN-β might be novel potential blood-based biomarkers in schizophrenia. The totality of these results also showed that HERV-W ENV facilitated antiviral innate immune response, resulting in neuronal apoptosis through the linc01930/cGAS/STING pathway in schizophrenia. Due to its monoclonal antibody GNbAC1 application in clinical trials, we considered HERV-W ENV might be a reliable therapeutic choice for schizophrenia.

Intergenic variants, rs1200114 and rs1200108 are genetically associated along with a decreased ATP1B1 expression in Fuchs Endothelial Corneal Dystrophy

Fuchs endothelial corneal dystrophy (FECD) is an age-related, bilateral corneal condition, characterized by apoptosis of the terminally differentiated endothelial cells. A genome-wide association study (GWAS) conducted in the European population in 2017, identified a new single nucleotide polymorphism (SNP), rs1200114 in the intergenic region between long intergenic non-protein coding RNA 970 (LINC00970) and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). The major focus of the current study is to understand the genetic association of this intergenic variant, rs1200114 with FECD in the Indian population. Sanger sequencing followed by statistical analysis indicated a significant difference in the allelic frequency between controls and cases (P = 0.01) with the minor allele ‘G’ of rs1200114 imparting a 1.64 fold increased risk for the disease. Luciferase reporter assay revealed no significant difference in the luciferase activity between allele ‘A’ and ‘G’ of rs1200114. However, quantitative RT-PCR assay revealed lower expression of ATP1B1 in FECD subjects compared with controls (P = 0.007). Therefore, to find whether another nearby SNP imparts regulatory effect, tag SNP association analysis was carried out; which revealed a significant association of another SNP, rs1200108, present in the intergenic region between LINC00970 and ATP1B1 with FECD (P = 0.009). The protective allele ‘A’ of rs1200108 displayed reduced reporter activity as opposed to the risk allele ‘G’ (P = 0.014). Furthermore, haplotype ‘A-A’ of rs1200108 - rs1200114 was present at a higher frequency in control subjects, suggesting it as a protective haplotype. Altogether, this study inferred the genetic association of rs1200114 and rs1200108 along with the decreased expression of ATP1B1 related to FECD pathogenesis in the Indian population.

LINC00173 facilitates tumor progression by stimulating RAB1B-mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma.

An increasing number of studies have found that long non-coding RNA (lncRNA) play important roles in driving the progression of nasopharyngeal carcinoma (NPC). Our microarray screening revealed that expression of the lncRNA long intergenic non-protein coding RNA 173 (LINC00173) was upregulated in NPC. However, its role and mechanism in NPC have not yet been elucidated. In this study, we demonstrate that high LINC00173 expression indicated a poor prognosis in NPC patients. Knockdown of LINC00173 significantly inhibited NPC cell proliferation, migration and invasion invitro. Mechanistically, LINC00173 interacted and colocalized with Ras-related protein Rab-1B (RAB1B) in the cytoplasm, but the modulation of LINC00173 expression did not affect the expression of RAB1B at either the mRNA or protein levels. Instead, relying on the stimulation of RAB1B, LINC00173 could facilitate the extracellular secretion of proliferation-associated 2G4 (PA2G4) and stromal cell-derived factor 4 (SDF4; also known as 45-kDa calcium-binding protein) proteins, and knockdown of these proteins could reverse the NPC aggressive phenotype induced by LINC00173 overexpression. Moreover, invivo LINC00173-knockdown models exhibited a marked slowdown in tumor growth and a significant reduction in lymph node and lung metastases. In summary, LINC00173 serves as a crucial driver for NPC progression, and the LINC00173-RAB1B-PA2G4/SDF4 axis might provide a potential therapeutic target for NPC patients.