Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275.
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ABSTRACT:
SUBMITTER: Feng J
PROVIDER: S-EPMC8806334 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.
| S-EPMC4418692 | biostudies-literature
Project description:GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual-luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR-137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.
| S-EPMC8173206 | biostudies-literature
Project description:PurposeCurrently, there is no efficient and feasible method for diffuse large B-cell lymphoma (DLBCL) in clinical practice, and the main reason is the unclear pathogenesis of DLBCL, which leads to a high fatality rate of DLBCL.MethodsTherefore, it is meaningful to explore the molecular mechanism of DLBCL and find a targeted therapeutic approach from the molecular level.ResultsLong non-coding RNA (lncRNA) SBF2-AS1 was highly expressed in DLBCL tissues and cell lines. Silencing of SBF2-AS1 inhibited the viability and growth of OCI-LY-3 cells. Furthermore, SBF2-AS1 acted as a sponge of miR-494-3p and inhibited its expression. And miR-494-3p directly targeted FGFR2. Functionally, forced expression of miR-494-3p or knockdown of FGFR2 removed the promoted effects of lncRNA SBF2-AS1 on DLBCL development. In vivo tumorigenesis experiments indicated SBF2-AS1 accelerated tumor growth via miR-494-3p/FGFR2 axis.ConclusionOur study revealed that SBF2-AS1 promoted the growth of DLBCL, which were mediated by miR-494-3p/FGFR2 axis.
| S-EPMC7837595 | biostudies-literature
Project description:Accumulating evidence has demonstrated that long noncoding RNA (lncRNA) is importantly related to the occurrence and development of cancer. According to reports, the expression of B3GALT5-AS1 in hepatocellular carcinoma (HCC) is downregulated; however, the role of B3GALT5-AS1 in HCC is not yet clear. In this study, our purpose is to explore the biological function of B3GALT5-AS1 in HCC and its coupling mechanism with miR-934 and ubiquitin-fold modifier 1 (UFM1). We found that the B3GALT5-AS1 expression level was of significant reduction in both HCC tissues and cell lines; B3GALT5-AS1 overexpression (ov) may inhibit the malignant features of HCC. In addition, we demonstrated that miR-934 mimics could reverse the effect of B3GALT5-AS1 ov, which proved miR-934 was the downstream regulator of B3GALT5-AS1. Furthermore, si-UFM1 could reverse the effect of miR-934 inhibitor, which revealed the connection between them. Moreover, we found that B3GALT5-AS1 could keep down the PI3K/AKT pathway through UFM1. Our results demonstrated that B3GALT5-AS1 was an excellent HCC suppressant by regulating miR-934 and UFM1 to achieve negative regulation of HCC cell proliferation, invasion, and metastasis, indicating that B3GALT5-AS1 is a promising potential therapeutic target for HCC treatment.
| S-EPMC8550832 | biostudies-literature
Project description:Increasing research has demonstrated that lncRNAs participate in the development of multiple cancer types. However, the role of TTN?AS1 in endometrial cancer (EC) remains unknown. The present study aimed to explore the function of titin?antisense RNA1 (TTN?AS1) in EC progression and the underlying mechanisms. qRT?PCR was performed to assess the TTN?AS1 expression patterns in EC tissues and cell lines. Loss of function experiments were carried out to estimate the effects of TTN?AS1 on EC cell proliferation, migration and invasion. To reveal the underlying mechanisms, informatics tools were used to predict the targets. Rescue experiments were performed to investigate the TTN?AS1?regulated miR?376a?3p/pumilio homolog 2 (PUM2) axis involved. The results of the present study revealed that TTN?AS1 was highly expressed in both EC tissues and cell lines, and TTN?AS1 knockdown inhibited EC cell proliferation, migration and invasion. With respect to the mechanisms, miR?376a?3p was revealed to be targeted by TTN?AS1, and reversed the effects on EC development induced by TTN?AS1. In addition, PUM2 was positively regulated by TTN?AS1, and miR?376a?3p mediated the regulation between them. Furtherly, in vivo experiments confirmed the results. Collectively, TTN?AS1 enhanced EC cell proliferation and metastasis by targeting the miR?376a?3p/PUM2 axis, which may shed light on EC diagnosis and treatment.
| S-EPMC7448418 | biostudies-literature
Project description:Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel ?-catenin-interacting protein and represses ?-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that ?-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced ?-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of ?-catenin-mediated nephrogenesis.
| S-EPMC3220563 | biostudies-literature
Project description:The two-component signal transduction pathways in bacteria use a histidine-aspartate phosphorelay circuit to mediate cellular changes in response to environmental stimuli. Here we describe a novel two-component todST system, which activates expression of the toluene degradation (tod) pathway in Pseudomonas putida F1. The todS gene is predicted to encode a sensory hybrid kinase with two unique properties--a basic region leucine zipper dimerization motif at the N terminus and a duplicated histidine kinase motif. Evidence from a synthetic peptide model suggests that TodS binds as a dimer to a pseudopalindromic sequence (5'-TGACTCA), which resembles the recognition sequence of the eukaryotic transcription factors Fos and Jun. These results provide additional evidence that bacteria and eukaryotes share common regulatory motifs. The todT gene product, a response regulator, was overproduced as a fusion protein in Escherichia coli, and the purified protein was found to bind specifically to a 6-bp palindromic DNA structure in the tod control region. The phosphorylated form of TodT appears to be the activator of tod structural genes. This is the first report of a two-component system that regulates aromatic metabolism in bacteria.
| S-EPMC19812 | biostudies-literature
Project description:AimsLong non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.MethodsUsing quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.ResultsThe expression of PCBP1-AS1 was pre-eminent in OP tissues and decreased throughout the development of human bone marrow-derived mesenchymal stem cells (hBMSCs) into osteoblasts. PCBP1-AS1 knockdown and overexpression respectively promoted and suppressed hBMSC proliferation and osteogenic differentiation capacity. Mechanistically, PCBP1-AS1 sponged miR-126-5p and consequently targeted PAK2. Inhibiting miR-126-5p significantly counteracted the beneficial effects of PCBP1-AS1 or PAK2 knockdown on hBMSCs' ability to differentiate into osteoblasts.ConclusionPCBP1-AS1 is responsible for the development of OP and promotes its progression by inducing PAK2 expression via competitively binding to miR-126-5p. PCBP1-AS1 may therefore be a new therapeutic target for OP patients.
| S-EPMC10259264 | biostudies-literature
Project description:Using an Lzts2 knock-out mouse model, we characterized the biological role of Lzts2 in tumorigenesis. Both heterozygous and homozygous deletion of the Lzts2-targeted allele in mice shows an increased incidence in spontaneous tumor development, although Lzts2 homozygous knock-out mice show significantly higher incidences than heterozygous mice. Treatment of Lzts2-deficient mice with a carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine, increases the susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinoma development. Examination of human prostate cancer tissue specimens shows a reduction of LZTS2 protein expression in prostate cancer cells. Further analyses of mouse embryonic fibroblasts isolated from Lzts2 knock-out embryos show that loss of Lzts2 enhances cell growth. These data provide the first line of evidence demonstrating that deletion of Lzts2 increases susceptibility to spontaneous and carcinogen-induced tumor development.
| S-EPMC3567628 | biostudies-literature
Project description:BackgroundLong non-coding RNA is considered to be essential to modulate the development and progression of human malignant cancers. And long non-coding RNA can act as crucial modulators by sponging the corresponding microRNA in tumorigenesis. We aimed to elucidate the function of ACTA2-AS1 and its molecular mechanism in colon adenocarcinoma.Materials and methodsThe expression of ACTA2-AS1, miR-4428 and BCL2L11 in colon adenocarcinoma tissues were detected via qRT-PCR. SW480 and HT29 cells were transfected with shRNA ACTA2-AS1, OE ACTA2-AS1, miRNA mimics of miR-4428, miR-4428 inhibitor, si-BCL2L11 and over-expression of si-BCL2L11. Cell proliferation, colony formation and apoptosis were respectively assessed using CCK-8 assay, colony assay and flow cytometry. Luciferase reporter assay was performed to verify the targets of ACTA2-AS1 and miR-4428. Tumor subcutaneous xenograft mode was constructed to explore tumor growth in vivo.ResultsACTA2-AS1 was obviously downregulated in human colon adenocarcinoma tissues and colon adenocarcinoma cell lines. Silence or over-expression of ACTA2-AS1 promoted or inhibited cell proliferation and colony formation abilities, and regulated apoptosis. The silence of ACTA2-AS1 resulted in the decrease of Bax and increase of Bal2, while restored in OE ACTA2-AS1 group when compared with the control transfected cells. In addition, luciferase reporter assay revealed that ACTA2-AS1 interacted with miR-4428 and suppressed its expression. miR-4428 could bind to 3' untranslated region of BCL2L11 and modulated the expression of BCL2L11 negatively. Knockdown of ACTA2-AS1 and over-expression of BCL2L11 reversed the biological function that ACTA2-AS1 mediated by knockdown ACTA2-AS1 alone.ConclusionOur data demonstrated that ACTA2-AS1 could suppress colon adenocarcinoma progression via sponging miR-4428 to regulate BCL2L11 expression.
| S-EPMC8042989 | biostudies-literature