LncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis.
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ABSTRACT:
SUBMITTER: Ni W
PROVIDER: S-EPMC8805943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment.
| S-EPMC7191191 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) remains one of the most lethal malignant tumors worldwide; however, the etiology of HCC still remains poorly understood. In the present study, cancer-omics databases, including The Cancer Genome Atlas, GTEx and Gene Expression Omnibus, were systematically analyzed in order to investigate the role of the long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2-antisense 1 (ZFPM2-AS1) and the zinc finger protein, FOG family member 2 (ZFPM2) gene in the occurrence and progression of HCC. It was identified that the expression levels of lncRNA ZFPM2-AS1 were significantly increased in HCC tissues, whereas expression levels of the ZFPM2 gene were significantly decreased in HCC tissues compared with normal liver tissues. Higher expression levels of ZFPM2-AS1 were significantly associated with a less favorable prognosis of HCC, whereas higher expression levels of the ZFPM2 gene were associated with a more favorable prognosis of HCC. Genetic alterations in the ZFPM2 gene may contribute to a worse prognosis of HCC. Validation of the GSE14520 dataset also demon stared that ZFPM2 gene expression levels were significantly decreased in HCC tissues (P<0.001). The receiver operating characteristic (ROC) analysis of the ZFPM2 gene indicated high accuracy of this gene in distinguishing between HCC tissues and non-tumor tissues. The areas under the ROC curves were >0.8. Using integrated strategies, the present study demonstrated that lncRNA ZFPM2-AS1 and the ZFPM2 gene may contribute to the occurrence and prognosis of HCC. These findings may provide a novel understanding of the molecular mechanisms underlying the occurrence and prognosis of HCC.
| S-EPMC7202276 | biostudies-literature
Project description:BackgroundZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma.MethodsDifferentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene in vivo.ResultsZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1.ConclusionZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma.
| S-EPMC8290669 | biostudies-literature
Project description:Accumulating evidences revealed that long noncoding RNAs (lncRNAs) have been participated in cancer malignant progression, including glioblastoma multiforme (GBM). Despite much studies have found the precise biological role in the regulatory mechanisms of GBM, however the molecular mechanisms, particularly upstream mechanisms still need further elucidated. RT-QPCR, cell transfection, western blotting and bioinformatic analysis were executed to detect the expression of EGR1, HNF1A-AS1, miR-22-3p and ENO1 in GBM. Cell proliferation assay, colony formation assay, wound healing, migration and invasion assays were performed to detect the malignant characters of GBM cells. The molecular regulation mechanism was confirmed by luciferase reporter assay, ChIP and RIP. Finally, orthotopic mouse models were established to examine the effect of HNF1A-AS1 in vivo. In the current study, we analyzed clinical samples to show that the HNF1A-AS1 expression is upregulated and associated with poor patient survival in GBM. Functional studies revealed that HNF1A-AS1 knockdown markedly inhibits malignant phenotypes of GBM cells, whereas overexpression of HNF1A-AS1 exerts opposite effect. Mechanistically, the transcription factor EGR1 forced the HNF1A-AS1 expression by directly binding the promoter region of HNF1A-AS1. Furthermore, combined bioinformatics analysis with our mechanistic work, using luciferase reporter assays and RIP, we first demonstrated that HNF1A-AS1 functions as a competing endogenous RNA (ceRNA) with miR-22-3p to regulate ENO1 expression in GBM cells. HNF1A-AS1 directly binds to miR-22-3p and significantly inhibits miR-22-3p expression, while ENO1 expression was increased. miR-22-3p inhibitor offsets the HNF1A-AS1 silencing induced suppression in malignant behaviors of GBM cells. ENO1 was verified as a direct target of miR-22-3p and its expression levels was negatively with the prognosis in GBM patients. Taken together, our study illuminated the definite mechanism of HNF1A-AS1 in promoting GBM malignancy, and provided a novel therapeutic target for further clinical application.
| S-EPMC8590016 | biostudies-literature
Project description:Long non‑coding RNAs (lncRNAs) and microRNAs (miRs) have been reported to regulate disease progression in numerous types of disease, including retinoblastoma (Rb). Therefore, the present study aimed to investigate the effects of the lncRNA FEZ family zinc finger 1 antisense RNA 1 (FEZF1‑AS1) on Rb and to determine its possible mechanism of action. Reverse transcription‑quantitative PCR and western blot analysis were conducted to detect the gene or protein expression. Cell Counting Kit‑8, wound healing and transwell invasion assays were performed to estimate the capabilities of cell viability, invasion and migration. The potential association between FEZF1‑AS1 and miR‑1236‑3p in Y79 cells was measured via dual‑luciferase reporter assay. The results of the present study revealed that the levels of FEZF1‑AS1 were significantly upregulated in different Rb cell lines, with the most prominent upregulation observed in Y79 cells. In addition, the cell viability, invasive and migratory abilities, and the ability to undergo epithelial‑mesenchymal transition (EMT), were significantly inhibited following the transfection of short hairpin RNA (shRNA)‑FEZF1‑AS1 into Y79 cells. Further experimental validation confirmed that miR‑1236‑3p may be a direct target of FEZF1‑AS1. Notably, the miR‑1236‑3p inhibitor was discovered to reverse the inhibitory effects of shRNA‑FEZF1‑AS1 on cell viability, invasion, migration and EMT. In conclusion, the findings of the present study suggested that lncRNA‑FEZF1‑AS1 may promote the viability, migration, invasion and EMT of Rb cells by modulating miR‑1236‑3p.
| S-EPMC7533456 | biostudies-literature
Project description:Breast phyllodes tumor (PT) is a rare fibroepithelial neoplasm with potential malignant behavior. Long non-coding RNAs (lncRNAs) play multifaceted roles in various cancers, but their involvement in breast PT remains largely unexplored. In this study, microarray was leveraged for the first time to investigate the role of lncRNA in PT. We identified lncRNA ZFPM2-AS1 was significantly upregulated in malignant PT, and its overexpression endowed PT with high tumor grade and adverse prognosis. Furthermore, we elucidated that ZFPM2-AS1 promotes the proliferation, migration, and invasion of malignant PT in vitro. Targeting ZFPM2-AS1 through nanomaterial-mediated siRNA delivery in patient-derived xenograft (PDX) model could effectively inhibit tumor progression in vivo. Mechanistically, our findings showed that ZFPM2-AS1 is competitively bound to CDC42, inhibiting ACK1 and STAT1 activation, thereby launching the transcription of TNFRSF19. In conclusion, our study provides evidence that ZFPM2-AS1 plays a pivotal role in the pathogenesis of breast PT, and suggests that ZFPM2-AS1 could serve as a prognostic indicator for patients with PT as well as a promising novel therapeutic target.
| S-EPMC11252458 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are implicated to be involved in the pathogenesis of many cancers. Herein we report on our discovery of a novel lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), and its critical role in gastric carcinogenesis. ZFPM2-AS1 expression in gastric cancer specimens was analyzed using Gene Expression Omnibus data set and validated in 73 paired gastric tumor and normal adjacent gastric tissue specimens using qRT-PCR. The effect of ZFPM2-AS1 expression on proliferation and apoptosis in gastric cancer cells was assessed by altering its expression in vitro and in vivo. Mechanistic investigation was carried out using cell and molecular biological approaches. ZFPM2-AS1 expression was higher in gastric tumors than in normal gastric tissue. Also, increased ZFPM2-AS1 expression in gastric cancer specimens was associated with tumor size, depth of tumor invasion, differentiation grade, and TNM stage. High ZFPM2-AS1 expression predicted markedly reduced overall and disease-free survival in gastric cancer patients. Functional experiments demonstrated that ZFPM2-AS1 expression promoted proliferation and suppressed apoptosis of gastric cancer cells in vitro and promoted tumor growth in vivo. This effect is associated with attenuated nuclear translocation of p53. Mechanistic experiments demonstrated that tumor-activated ZFPM2-AS1 could bind to and protect the degradation of macrophage migration inhibitory factor (MIF), a potent destabilizer of p53. Knockdown of MIF expression diminished ZFPM2-AS1's impact on p53 expression in gastric cancer cells. Our findings demonstrated that ZFPM2-AS1 regulates gastric cancer progression and revealed a novel ZFPM2-AS1/MIF/p53 signaling axis, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant gastric cells.
| S-EPMC6226322 | biostudies-literature
Project description:Background:Oral squamous cell carcinoma (OSCC) is a common kind of squamous cell carcinoma of the head and neck, which is a threat to public health. Long noncoding RNAs (lncRNAs) are associated with the development of various diseases, including cancers. LncRNA titin antisense RNA 1 (TTN-AS1) is known as a crucial regulatory factor in several cancers. Nevertheless, the specific functions of TTN-AS1 in OSCC remains obscure. Methods:The expression of TTN-AS1 in OSCC samples or cells was analyzed through qRT-PCR. Colony formation assay, EdU assay, flow cytometry assay, TUNEL assay and wound healing assay were conducted to estimate the functions of TTN-AS1 in OSCC cells. RIP and luciferase reporter assays were utilized to detect the interaction between TTN-AS1 and miR-411-3p as well as between miR-411-3p and NFAT5. Results:TTN-AS1 expression was stronger in OSCC cells. Knockdown of TTN-AS1 effectively restrained cell proliferation and migration but had inductive role in apoptosis. Moreover, TTN-AS1 could function as the miR-411-3p sponge in OSCC and miR-411-3p exerted the inhibitory functions on OSCC cell growth. In addition, NFAT5 was proven as the target of miR-411-3p. Rescue assay indicated that overexpressing NFAT5 could reverse the inhibitory function of TTN-AS1 depletion on cell growth. Conclusion:lncRNA TTN-AS1 contributed to the progression of OSCC via miR-411-3p/NFAT5 axis.
| S-EPMC7453543 | biostudies-literature
Project description:Aberrant expressions of various long non-coding RNAs (lncRNAs) have been involved in the progression and pathogenesis of various carcinomas. However, the expression and biological function of SLCO4A1-AS1 in colorectal cancer (CRC) remain poorly understood. Gain- and loss-of-function assays were applied to determine the roles of SLCO4A1-AS1 in autophagy and CRC progression. qRT-PCR and in situ hybridization (ISH) results showed that SLCO4A1-AS1 was positively associated with PARD3 expression in CRC tissues. In vitro and in vivo studies revealed that SLCO4A1-AS1 knockdown repressed cytoprotective autophagy as assayed by transmission electron microscopy (TEM), and inhibited cell proliferation by directly targeting partition-defective 3 (PARD3). Mechanistically, SLCO4A1-AS1 acted as a sponge of miR-508-3p, leading to upregulation of PARD3 and promotion of CRC cell proliferation. The current study demonstrates that the SLCO4A1-AS1/miR-508-3p/PARD3/autophagy pathway play a critical role in CRC cell proliferation, and might provide novel targets for developing therapeutic strategies for CRC.
| S-EPMC6682525 | biostudies-literature
Project description:BackgroundLncRNA was known to be closely associated with the progression of human tumors. The role of lncRNA LIFR-AS1 in the pathogenesis and progression of gastric tumor is still unclear. The aim of this study was to investigate the function of LIFR-AS1 and the underlying mechanism in the pathogenesis and progression of gastric cancer.MethodsQRT-PCR was used to evaluate the expression of LIFR-AS1, miR-29a-3p and COL1A2 in gastric tumor tissues and cells. Western blotting was used to evaluate the protein expression of COL1A2 in gastric tumor cells. CCK-8 assay, transwell assay and flow cytometry were used to evaluate the roles of LIFR-AS1, miR-29a-3p and COL1A2 in cell proliferation, invasion, migration and apoptosis. The relationship among LIFR-AS1, miR-29a-3p and COL1A2 was assessed by bioinformatics analyses and luciferase reporter assay.ResultsThe expression levels of LIFR-AS1 were significantly increased in gastric tumor tissues and cells, while the expression levels of miR-29a-3p were decreased. The expression of miR-29a-3p was negatively correlated with the expression of LIFR-AS1 in gastric cancer tumor tissues. Knocking down of LIFR-AS1 inhibited proliferation, invasion and migration of gastric tumor cells, and induced apoptosis of gastric tumor cells. Bioinformatics analyses and integrated experiments revealed that LIFR-AS1 elevated the expression of COL1A2 through sponging miR-29a-3p, which further resulted in the progression of gastric tumor.ConclusionLIFR-AS1 plays an important role as a competing endogenous RNA in gastric tumor pathogenesis and may be a potential target for the diagnosis and treatment of gastric tumor.
| S-EPMC7789183 | biostudies-literature