KCNQ1 Opposite Strand/antisense Transcript 1 Research Articles

Long non-coding RNA KCNQ1 opposite strand/antisense transcript 1, a potential biomarker for glaucoma, accelerates glaucoma progression via microRNA-93-5p/Homeobox box 3 axis

BackgroundGlaucoma is marked by retinal neuron death in the ganglion cell layer, leading to irreversible vision loss. Aberrant long non-coding RNA (lncRNA) expression is associated with glaucoma. The study was to explore the latent molecular mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in N-methyl-D-aspartate (NMDA)-stimulated glaucoma. ResultsThe data demonstrated that KCNQ1OT1 expression was elevated in glaucoma patients, serving as a diagnostic biomarker of glaucoma. Rats injected with NMDA developed visual loss and retinopathy and expressed high KCNQ1OT1. After treating retinal ganglion cells (RGCs) with NMDA, cell proliferation was suppressed and apoptosis was augmented. Silenced KCNQ1OT1 or HOXB3 or elevated miR-93-5p alleviated NMDA-induced suppression of RGC growth. KCNQ1OT1 mediated miR-93-5p expression by targeting homeobox box 3 (HOXB3). The protection of silenced KCNQ1OT1 in NMDA-treated RGCs was turned around by elevated HOXB3. ConclusionsOverall, KCNQ1OT1 accelerates glaucoma progression via miR-93-5p/HOXB3 axis.How to cite: Xie ZL, Wang H, Liu LL, et al. Long non-coding RNA KCNQ1 opposite strand/antisense transcript 1, a potential biomarker for glaucoma, accelerates glaucoma progression via microRNA-93-5p/Homeobox box 3 axis. Electron J Biotechnol 2024;67 . https://doi.org/10.1016/j.ejbt.2023.10.002.

LncRNA KCNQ1OT1 contributes to hydrogen peroxide-induced apoptosis, inflammation, and oxidative stress of cardiomyocytes via miR-130a-3p/ZNF791 axis.

It has been reported that long noncoding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) played an important role in myocardial infarction (MI). However, the regulatory network behind KCNQ1OT1 in MI is largely unknown. Quantitative real time polymerase chain reaction (qRT-PCR) was applied to detect the enrichment of KCNQ1OT1, microRNA-130a-3p (miR-130a-3p) and zinc finger 791 (ZNF791). The viability and apoptosis of AC16 cells were measured by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was conducted to assess the inflammation and oxidative stress status of AC16 cells. The targeted relationship between miR-130a-3p and KCNQ1OT1 or ZNF791 was predicted by StarBase bioinformatic database, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to verify these predictions. Hydrogen peroxide (H2 O2 ) stimulation caused a significant upregulation in the expression of KCNQ1OT1, while the level of miR-130a-3p showed an opposite phenomenon. KCNQ1OT1 was a crucial downstream component in H2 O2 -mediated toxic effects, and KCNQ1OT1 accelerated H2 O2 -induced toxic effects in AC16 cells. KCNQ1OT1 could sponge miR-130a-3p and down-regulate its expression. MiR-130a-3p exerted opposite effects to KCNQ1OT1, and the depletion of miR-130a-3p attenuated the protective effects of KCNQ1OT1 intervention on AC16 cells exposed to H2 O2 . MiR-130a-3p could bind to ZNF791, and ZNF791 served as the target of miR-130a-3p to promote H2 O2 -induced injury of AC16 cells. ZNF791 was modulated by KCNQ1OT1/miR-130a-3p signaling in H2 O2 -treated AC16 cells. In all, lncRNA KCNQ1OT1 deteriorated H2 O2 -mediated injury in cardiomyocytes through upregulating ZNF791 via serving as a molecular sponge for miR-130a-3p.

LncRNA KCNQ1OT1 attenuates myocardial injury induced by hip fracture via regulating of miR-224-3p/GATA4 axis

ObjectiveThis article aims to discuss the role of l KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in myocardial injury caused by a hip fracture and further investigate its potential molecular mechanisms. MethodsX-Ray and H&E staining are used to observe hip fracture and pathological changes of myocardial tissue. ELISA and kits are used to detect inflammatory cytokines, lactate dehydrogenase (LDH), and creatine kinase (CK) in serum. The proliferation and apoptosis of H9c2 are determined by CCK-8 and flow cytometry. RT-qPCR and Western blot are applied to quantitatively assess the expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-224-3p. Furthermore, the interaction is verified by a luciferase reporter assay. ResultsA hip fracture model was successfully established. The high expression of inflammatory cytokines and cardiac injury markers indicated that hip fracture successfully induced myocardial injury. In TNF-ɑ treated cardiomyocyte model, high expression of KCNQ1OT1 promoted H9c2 cell proliferation and inhibited apoptosis. Furthermore, in the myocardial injury model rats induced by hip fracture, a high expression of KCNQ1OT1 reduced pathological damage in the myocardial tissue. Further research illustrated that miR-224-3p was the direct target of KCNQ1OT1, and GATA4 was the direct target of miR-224-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated myocardial injury caused by hip fracture via targeting the miR-224-3p/GATA4 axis. ConclusionOur study demonstrates that the KCNQ1OT1 suppresses myocardial injury via mediating miR-224-3p/GATA4, which provides a latent target for myocardial injury treatment.

Curcumin Suppresses TGF-β2-Induced Proliferation, Migration, and Invasion in Lens Epithelial Cells by Targeting KCNQ1OT1/miR-377-3p/COL1A2 Axis in Posterior Capsule Opacification

Purpose: Posterior capsule opacification (PCO) is a common complication after cataract surgery, which can lead to secondary loss of vision. Curcumin has been reported to play a suppressive role in PCO progression, and the potential molecular mechanism was explored in this study. Methods: Cell viability and proliferation were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay. Transwell assay and wound healing assay were performed to assess cell invasion and migration abilities. Western blot assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were conducted to measure the expression of proteins and RNAs. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to confirm the interaction between microRNA-377-3p (miR-377-3p) and KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) or collagen type I alpha 2 chain (COL1A2). Results: Curcumin dose-dependently alleviated transforming growth factor-β2 (TGF-β2)-induced proliferation, migration, and invasion in SRA01/04 cells. KCNQ1OT1 was up-regulated in PCO patients and TGF-β2-induced SRA01/04 cells. Curcumin-induced protective effects in TGF-β2-induced SRA01/04 cells were largely overturned by KCNQ1OT1 overexpression. KCNQ1OT1 directly interacted with miR-377-3p and negatively regulated its expression. miR-377-3p silencing overturned Curcumin-mediated protective effects in SRA01/04 cells upon TGF-β2 treatment. miR-377-3p directly interacted with the 3’ untranslated region (3’UTR) of COL1A2. COL1A2 overexpression largely counteracted KCNQ1OT1 silencing-induced effects in TGF-β2-stimulated SRA01/04 cells. KCNQ1OT1 could up-regulate COL1A2 expression by sponging miR-377-3p in SRA01/04 cells. Conclusion: In conclusion, Curcumin suppressed TGF-β2-induced malignant changes in lens epithelial cells by targeting KCNQ1OT1/miR-377-3p/COL1A2 axis.

KCNQ1OT1 inhibition alleviates high glucose-induced podocyte injury by adsorbing miR-23b-3p and regulating Sema3A.

Diabetic nephropathy (DN), a diabetic complication, is the leading cause of end-stage renal disease. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), a long non-coding RNA, has been unmasked to participate in the pathogenesis of DN. However, the specific mechanism by which KCNQ1OT1 regulates podocyte injury remains unclear. Relative expression of KCNQ1OT1 was measured with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines were analyzed by enzyme linked immunosorbent assay (ELISA). The viability, proliferation, and apoptosis of high glucose (HG)-treated podocyte were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Protein levels were analyzed by western blotting. The regulatory mechanism of KCNQ1OT1 was surveyed by bioinformatics analysis, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays. We observed an apparent upregulation in KCNQ1OT1 expression in serums of DN patients and HG-treated podocytes. Furthermore, KCNQ1OT1 downregulation alleviated HG-induced inflammation, proliferation repression, and apoptosis in podocytes. Notably, KCNQ1OT1 was identified as a miR-23b-3p sponge, and miR-23b-3p directly targeted Semaphorin-3A (Sema3A). Moreover, miR-23b-3p silencing reversed KCNQ1OT1 knockdown-mediated effects on inflammation, proliferation, and apoptosis of HG-induced podocytes. Also, Sema3A overexpression reversed the effects of miR-23b-3p mimic on inflammation, proliferation, and apoptosis of HG-induced podocytes. Importantly, KCNQ1OT1 regulated Sema3A expression by sponging miR-23b-3p. HG-induced KCNQ1OT1 promoted inflammation, proliferation repression, and apoptosis of podocytes via increasing Sema3A expression through sponging miR-23b-3p. This study provided evidence to support the involvement of KCNQ1OT1 in the pathogenesis of DN.

KCNQ1OT1: An Oncogenic Long Noncoding RNA.

Long noncoding RNAs (lncRNAs) are transcripts greater than 200 nucleotides that do not code for proteins but regulate gene expression. Recent studies indicate that lncRNAs are involved in the modulation of biological functions in human disease. KCNQ1 Opposite Strand/Antisense Transcript 1 (KCNQ1OT1) encodes a lncRNA from the opposite strand of KCNQ1 in the CDKN1C/KCNQ1OT1 cluster that is reported to play a vital role in the development and progression of cancer. KCNQ1OT1 regulates cancer cell proliferation, cell cycle, migration and invasion, metastasis, glucose metabolism, and immune evasion. The aberrant expression of KCNQ1OT1 in cancer patients is associated with poor prognosis and decreased survival. This review summarizes recent literature related to the biological functions and molecular mechanisms of KCNQ1OT1 in various human cancers, including colorectal, bladder, breast, oral, melanoma, osteosarcoma, lung, glioma, ovarian, liver, acute myeloid leukemia, prostate, and gastric. We also discuss the role of KCNQ1OT1 as a promising diagnostic biomarker and a novel therapeutic target in human cancers.

LncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR‑223‑3p.

Atrial fibrillation (AF) is one of the most common forms of cardiac arrhythmia. Novel evidence has indicated that a competing endogenous RNA (ceRNA) mechanism may occur in AF. The present study aimed to identify differentially expressed microRNAs (miRNAs/miRs) in AF and predict their targeting long non-coding RNAs (lncRNAs) to identify a potential ceRNA network involved in AF using bioinformatics analysis. The GSE68475 microarray dataset was downloaded from the Gene Expression Omnibus database and differentially expressed miRNAs in AF were obtained. In addition, right atrial appendage (RAA) tissues from patients with AF were collected to determine the expression levels of the miRNAs identified following bioinformatics analysis using reverse transcription-quantitative PCR (n=8 per group). Subsequently, Gene Ontology (GO) functional term and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses of the target genes of differentially expressed miRNAs of interest were performed. The potential upstream lncRNAs targeting the identified miRNAs were predicted using bioinformatics analysis. A dual luciferase reporter assay was used to verify the existence of a targeted relationship between the differentially expressed miRNA and lncRNA of interest. The results identified 43 differentially expressed miRNAs, including 23 upregulated miRNAs. The trends in the expression levels of miR-223-3p were inconsistent between the microarray data and those recorded in the RAA tissues from patients with persistent AF. Therefore, miR-223-3p was selected as the miRNA of interest for further investigations. The target gene of miR-233-3p was found to be enriched in 57 GO terms and 21 KEGG signaling pathways. According to the bioinformatics prediction, 69 lncRNAs targeting miR-223-3p were identified, including the lncRNA growth arrest-specific transcript 5, lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and lncRNA MYC-induced long non-coding RNA. The results from dual luciferase assay confirmed that miR-223-3p was a direct target of KCNQ1OT1. A ceRNA regulatory relationship may exist between KCNQ1OT1 and miR-223-3p in AF, providing therefore a novel potential research target for further studies.

LncRNA KCNQ1OT1 promotes the development of diabetic nephropathy by regulating miR-93-5p/ROCK2 axis

BackgroundLong non-coding RNAs (lncRNAs) have been reported to play vital roles in diabetic nephropathy (DN). The aim of this study was to explore the function of mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in DN.MethodsDN cell models were established using high glucose (HG) treatment in human glomerular mesangial cells (HGMC) and human renal glomerular endothelial cells (HRGEC). The expression levels of KCNQ1OT1, microRNA-93-5p (miR-93-5p), and Rho associated coiled-coil containing protein kinase 2 (ROCK2) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. ROCK2 and apoptosis/fibrosis-related protein levels were examined by western blot. The predicted interaction between miR-93-5p and KCNQ1OT1 or ROCK2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.ResultsKCNQ1OT1 was upregulated in DN patients and DN cell models. KCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN cell models. MiR-93-5p was a direct target of KCNQ1OT1, and miR-93-5p inhibition restored the KCNQ1OT1 knockdown-mediated effects on cell proliferation, fibrosis and apoptosis in DN cell models. In addition, ROCK2 was identified as a target of miR-93-5p, and miR-93-5p overexpression suppressed cell proliferation and fibrosis and accelerated apoptosis by targeting ROCK2 in DN cell models. Moreover, KCNQ1OT1 regulated ROCK2 expression by binding to miR-93-5p.ConclusionKCNQ1OT1 knockdown inhibited cell proliferation and fibrosis and induced apoptosis in DN by regulating miR-93-5p/ROCK2 axis, providing potential value for the treatment of DN.

Long non-coding RNA KCNQ1OT1 promotes hydrogen peroxide-induced lens epithelial cell apoptosis and oxidative stress by regulating miR-223-3p/BCL2L2 axis

Many long non-coding RNAs (lncRNAs) can exert crucial roles in the pathogenesis of cataract, including lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1). We aimed to further elucidate the biological role and regulatory molecular mechanism of KCNQ1OT1 in cataract. The expression of KCNQ1OT1 and miR-223-3p and BCL2 like 2 (BCL2L2) was examined by qRT-PCR. Cataract cell model was constructed by treatment with hydrogen peroxide (H2O2) in lens epithelial cells (SRA01/04). SRA01/04 cell viability and cell apoptosis were tested using CCK-8 assay and flow cytometry, respectively. Western blot (WB) was performed to measure the levels of apoptosis-related proteins and BCL2L2 protein. The oxidative stress factors were analyzed by corresponding kits. The interaction between miR-223-3p and KCNQ1OT1 or BCL2L2 was validated by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. We found that KCNQ1OT1 was upregulated in cataract anterior lens capsule samples and H2O2-induced SRA01/04 cells. Knockdown of KCNQ1OT1 suppressed H2O2-induced SRA01/04 cell apoptosis and oxidative stress. KCNQ1OT1 acted as a sponge of miR-223-3p. Inhibition of miR-223-3p could abate the function of KCNQ1OT1 silence in H2O2-treated SRA01/04 cells. Additionally, BCL2L2 was a direct target of miR-223-3p, and miR-223-3p weakened H2O2-induced SRA01/04 cell apoptosis and oxidative stress by targeting BCL2L2. Collectively, the data suggest a role for the KCNQ1OT1/miR-223-3p/BCL2L2 axis in cataract formation but the data was generated using an epithelial cell line.

Knockdown of long non-coding RNA KCNQ1OT1 suppresses the progression of osteoarthritis by mediating the miR-211-5p/TCF4 axis in vitro.

Numerous studies have reported the critical roles of long non-coding RNAs (lncRNAs) in the regulation of osteoarthritis (OA) development. The present study aimed to assess the function and regulatory mechanism of a lncRNA, KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), in OA in vitro. C28/I2 cells were treated with lipopolysaccharide (LPS) to generate an in vitro OA model. The relative expression levels of KCNQ1OT1, microRNA (miR)-211-5p and transcription factor 4 (TCF4) were determined via reverse transcription-quantitative polymerase chain reaction. The associations between KCNQ1OT1, miR-211-5p and TCF4 were confirmed using a dual-luciferase reporter assay. Furthermore, cell viability was assessed using the MTT assay. Inflammatory cytokine levels were measured using ELISA. The protein expression levels of matrix metalloproteinase-3/13, collagen II/X and TCF4 were detected by western blotting. KCNQ1OT1 and TCF4 were highly expressed in the cartilage tissues of patients with OA and C28/I2 cells treated with LPS (OA cells), whereas miR-211-5p was downregulated concomitantly in OA tissues and cells. Knockdown of KCNQ1OT1 stimulated cell viability, and suppressed the inflammation and degradation of the extracellular matrix (ECM) in OA cells. In addition, overexpression of miR-211-5p stimulated cell viability, and inhibited inflammation and degradation of the ECM in OA cells. Notably, miR-211-5p was revealed to be the target of, and was negatively regulated by, KCNQ1OT1. TCF4 was targeted and negatively modulated by miR-211-5p. Transfection of cells with the miR-211-5p inhibitor or pcDNA-TCF4 reversed the suppressive effects of short hairpin RNA (sh)-KCNQ1OT1 on inflammation and ECM degradation, as well as the promotive effect of sh-KCNQ1OT1 on viability in OA in vitro. Therefore, KCNQ1OT1 may regulate the miR-211-5p/TCF4 axis to ameliorate OA in vitro.

Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis.

Long non-coding RNAs serve an essential role in drug resistance in various types of cancer, including lung, breast and bladder cancer. The present study aimed to investigate whether KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was associated with cisplatin (DDP) resistance in nasopharyngeal carcinoma (NPC). KCNQ1OT1, microRNA (miR)-454 and ubiquitin specific peptidase 47 (USP47) expression levels were measured via reverse transcription-quantitative PCR. 5-8F/DDP and SUNE-1/DDP cell viability and chemosensitivity were assessed by performing Cell Counting Kit-8 assays. Colony forming and Transwell assays were conducted to assess the effect of the KCNQ1OT1/miR-454/USP47 axis on DDP resistance in NPC cells. The association between miR-454 and KCNQ1OT1 or USP47 was verified via bioinformatics analysis, dual-luciferase reporter assays and RIP assays. KCNQ1OT1 and USP47 expression levels were significantly upregulated, whereas miR-454 expression levels were significantly downregulated in DDP-resistant NPC cells compared with parental NPC cells. KCNQ1OT1 knockdown promoted chemosensitivity in DDP-resistant NPC cells (5-8F/DDP and SUNE-1/DDP), as indicated by significantly decreased cell proliferation, migration and invasion in the short hairpin RNA (sh)KCNQ1OT1 group compared with the sh-negative control (NC) group. Moreover, miR-454 was identified as a target of KCNQ1OT1. KCNQ1OT1 overexpression significantly reversed miR-454 overexpression-mediated effects on NPC cell viability and DDP resistance. Furthermore, the results indicated that miR-454 directly targeted USP47. Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was significantly reversed by co-transfection with miR-454 inhibitor. Furthermore, compared with the shNC group, KCNQ1OT1 knockdown significantly downregulated USP47 expression, which was significantly counteracted by miR-454 knockdown. Collectively, the results of the present study indicated that KCNQ1OT1 enhanced DDP resistance in NPC cells via the miR-454/USP47 axis, suggesting a potential therapeutic target for patients with DDP-resistant NPC.

LncRNA KCNQ1OT1 acts as miR-216b-5p sponge to promote colorectal cancer progression via up-regulating ZNF146.

Long non-coding RNAs (lncRNAs) have shown to act as important regulators in cancer biology. The aim of this study was to investigate the role and mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in colorectal cancer (CRC) progression. The abundance of KCNQ1OT1, microRNA-216b-5p (miR-216b-5p) and zinc finger protein 146 (ZNF146) messenger RNA (mRNA) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Cell migration and invasion abilities were assessed by transwell assays. Western blot assay was performed for determination of protein levels. LncBase v.2 of DIANA Tool and StarBase software were used to predict the targets of KCNQ1OT1 and miR-216b-5p, respectively. Dual-luciferase reporter assay was implemented to confirm the target interaction between miR-216b-5p and KCNQ1OT1 or ZNF146. KCNQ1OT1 expression was higher in CRC tissues and cell lines. KCNQ1OT1 interference restrained the proliferation, migration and invasion of CRC cells. MiR-216b-5p was a target of KCNQ1OT1 in CRC cells, and KCNQ1OT1 knockdown-induced effects in CRC cells were partly overturned by miR-216b-5p silencing. MiR-216b-5p bound to the 3' untranslated region (3'UTR) of ZNF146, and ZNF146 overexpression partly attenuated miR-216b-5p overexpression-mediated influences in CRC cells. KCNQ1OT1 up-regulated the abundance of ZNF146 through sequestering miR-216b-5p in CRC cells. KCNQ1OT1 accelerated the proliferation and motility of CRC cells through elevating ZNF146 expression via sponging miR-216b-5p. KCNQ1OT1/miR-216b-5p/ZNF146 axis might be underlying target for the diagnosis and treatment of CRC patients.

LncRNA KCNQ1OT1 reverses the effect of sevoflurane on hepatocellular carcinoma progression via regulating the miR-29a-3p/CBX3 axis.

Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.

LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF.

ObjectiveWidely used in anesthesia, ketamine is reported to induce neurotoxicity in patients. This study aimed to investigate the molecular regulatory mechanism of long non-coding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in ameliorating ketamine-induced neural injury.Materials and MethodsSprague–Dawley rats were intraperitoneally injected with ketamine to induce neuronal injury. PC-12 cells treated with ketamine were used as the cell model. Ketamine-induced aberrant expression of KCNQ1OT1, miR-206 and brain-derived neurotrophic factor (BDNF) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of KCNQ1OT1 and miR-206 on ketamine-induced neural injury in PC-12 cells were then examined by MTT and LDH assay. The regulatory relationships between KCNQ1OT1 and miR-206, and miR-206 and BDNF were detected by dual-luciferase reporter assay.ResultsKetamine induced the apoptosis of neurons of the hippocampus in rats, and the apoptosis of PC-12 cells, accompanied by down-regulation of KCNQ1OT1 and BDNF expressions, and up-regulation of miR-206 expression. Overexpression of KCNQ1OT1 enhanced the resistance to apoptosis of PC-12 cells and significantly ameliorated ketamine-induced nerve injury, while transfection of miR-206 had opposite effects. Mechanistically, KCNQ1OT1 could target miR-206 and reduce its expression level, in turn indirectly increase the expression level of BDNF, and play a protective role in neural injury.ConclusionKCNQ1OT1/miR-206/BDNF axis is demonstrated to be an important regulatory mechanism in regulating ketamine-induced neural injury. Our study helps to clarify the mechanism by which ketamine exerts its toxicological effects and provides clues for the neuroprotection during anesthesia.

LncRNA KCNQ1OT1 promotes the proliferation, migration and invasion of retinoblastoma cells by upregulating HIF-1α via sponging miR-153-3p

It is reported that lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) is oncogenic in many cancers. This work aimed at probing into its expression and biological functions in retinoblastoma (RB)...

Sevoflurane Suppresses Glioma Cell Proliferation, Migration, and Invasion Both In Vitro and In Vivo Partially Via Regulating KCNQ1OT1/miR-146b-5p/STC1 Axis.

Background: Sevoflurane (Sev), a volatile anesthetic agent, is widely used in neurosurgery for anesthesia maintenance, accompanied with antitumor activity postanesthesia in multiple human cancers, including glioma. However, the molecular mechanism hidden in Sev in glioma is largely unclear, including associated informative noncoding RNAs, such as long noncoding RNAs (lncRNA) and microRNAs (miRNAs). Methods: Expression of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), miRNA (miR)-146b-5p, and stanniocalcin-1 (STC1) was measured by real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, apoptosis, migration, and invasion in vitro were examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, fluorescence-activated cell sorting method, and transwell assays, respectively. Tumor growth in vivo was determined by xenograft models. The direct interaction between genes was confirmed by dual-luciferase reporter assay. Results: Sev enhanced apoptotic rate, but inhibited cell viability, migration, and invasion abilities of human glioma A172 and U251 cells in vitro, as well as tumor growth inhibition in vivo. The tumor-suppressive role of Sev in glioma was accompanied with downregulated KCNQ1OT1 and STC1, and upregulated miR-146b-5p. Overexpression of KCNQ1OT1 through transfection reversed, while KCNQ1OT1 silencing aggravated the antitumor role of Sev in A172 and U251 cells. Moreover, KCNQ1OT1-mediated tumor-promoting activity in A172 and U251 cells under Sev treatment was abrogated by miR-146b-5p restoration or STC1 deletion. Essentially, KCNQ1OT1 could positively regulate STC1 by acting as miR-146b-5p decoy. Conclusion: KCNQ1OT1 knockdown mediated the role of Sev in glioma cell proliferation, apoptosis, migration, and invasion both in vitro and in vivo through miR-146b-5p/STC1 pathway.

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-\u0138B pathway in diabetic nephropathy

BackgroundIt has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism.MethodsHuman glomerular mesangial cells (HGMCs) and human renal glomerular endothelial cells (HRGECs) were cultured in high glucose (30 mM) condition as models of DN cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and miR-18b-5p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA and protein levels of Sorbin and SH3 domain-containing protein 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta 1 (TGF-β1), Twist, NF-κB and STAT3 were measured by qRT-PCR and western blot. Cell viability was detected by cell counting kit-8 (CCK-8) assay for selecting the proper concentration of glucose treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were employed to determine cell proliferation and apoptosis, respectively. The targets of KCNQ1OT1 was predicted by online software and confirmed by dual-luciferase reporter assay.ResultsKCNQ1OT1 and SORBS2 were elevated in DN. Both knockdown of KCNQ1OT1 and silencing of SORBS2 restrained proliferation and fibrosis and induced apoptosis in DN cells. Besides, Overexpression of SORBS2 restored the KCNQ1OT1 knockdown-mediate effects on proliferation, apoptosis and fibrosis in DN cells. In addition, miR-18b-5p served as a target of KCNQ1OT1 as well as targeted SORBS2. KCNQ1OT1 knockdown repressed NF-ĸB pathway.ConclusionKCNQ1OT1 regulated DN cells proliferation, apoptosis and fibrosis via KCNQ1OT1/miR-18b-5p/SORBS2 axis and NF-ĸB pathway.

LncRNA KCNQ1OT1 facilitates the progression of bladder cancer by targeting MiR-218-5p/HS3ST3B1.

Long non-coding RNA (lncRNA) is characterized by biological function in diverse cancers. LncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) is well acknowledged to regulate various cancers, while its role in bladder cancer remains unclear. In the present study, we aimed at probing into the impact and detailed mechanisms of KCNQ1OT1 in bladder cancer progression. In this study, we demonstrated that KCNQ1OT1 expression in bladder cancer tissues was notably up-regulated compared with in normal adjacent tissues, and KCNQ1OT1 modulated the malignant phenotypes of bladder cancer cells. Moreover, it was validated that KCNQ1OT1 could specifically bind to miR-218-5p and reduce its expression. Overexpressed miR-218-5p would inhibit the proliferation and metastasis of bladder cancer cells while facilitating apoptosis. In terms of Mechanism, Heparan Sulfate-Glucosamine 3-Sulfotransferase 3B1 (HS3ST3B1) was validated as a target gene of miR-218-5p, and could be regulated by KCNQ1OT1 indirectly. In conclusion, KCNQ1OT1 can promote the progression of bladder cancer through regulation of miR-218-5p/HS3ST3B1, which is expected to serve as a new therapeutic target for bladder cancer.

WITHDRAWN: LncRNA KCNQ1OT1 promotes cisplatin resistance of osteosarcoma cancer cells through the miR-335–5p/β-catenin axis

Abstract Long noncoding RNA (lncRNA) KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) has been shown to participate in the tumorigenesis of several types of cancers. However, little is known about the role of KCNQ1OT1 in the chemoresistance of osteosarcoma (OS). In this study, we concentrated on the function and mechanism of KCNQ1OT1 in cisplatin resistance of OS cells. We demonstrated that KCNQ1OT1 levels were upregulated in cisplatin-resistant OS tissues and cell lines. Moreover, knockdown of KCNQ1OT1 inhibited cell proliferation, migration, and invasion and decreased cisplatin resistance in osteosarcoma 143B cells. Additionally, bioinformatics analysis and dual-luciferase reporter assays showed that miR-335-5p directly targeted KCNQ1OT1 and the 3′-UTR of β-catenin mRNA, indicating that KCNQ1OT1 regulated the expression of β-catenin via endogenous sponging of miR-335-5p. Overall, KCNQ1OT1 modulated cisplatin resistance in OS through the miR-335-5p/β-catenin axis, indicating that KCNQ1OT1 aggravates OS progression and chemoresistance to cisplatin through induction of β-catenin expression by adsorbing miR-335-5p in cisplatin-resistant OS cells, providing a theoretical basis for the treatment of chemoresistant OS.

Long noncoding RNA KCNQ1OT1 is correlated with human breast cancer cell development through inverse regulation of hsa-miR-107.

In this work, we investigated the expression pattern and regulatory function of long noncoding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in breast cancer. We found that KCNQ1OT1 was significantly upregulated in breast cancer cell lines. In lentiviral-transduced BT-549 and HCC1599 cells, KCNQ1OT1 knockdown impaired cancer cell functions, including in vitro proliferation and migration, and in vivo transplant growth. The possible sponging target of KCNQ1OT1, human microRNA-107 (hsa-miR-107), was confirmed to be bound by KCNQ1OT1, and was upregulated in breast cancer cells with KCNQ1OT1 downregulation. Further, hsa-miR-107 knockdown in KCNQ1OT1-downregulated cancer cells reversed its impairing effects on cancer cell proliferation and migration in vitro. Thus, loss of KCNQ1OT1 is associated with functional impairment in breast cancer cells, likely through inverse regulation of its sponging target, hsa-miR-107.