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LncRNA IUR upregulates miR-34a to inhibit pancreatic adenocarcinoma cell migratory and invasive abilities.

ABSTRACT: The long non-coding RNA (lncRNA) imatinib-upregulated (IUR) has been recently reported as a tumor suppressor in leukemia. Preliminary microarray data revealed a downregulation of IUR in pancreatic adenocarcinoma (PAAD) and a positive correlation with microRNA-34a (miR-34a) expression. The present study aimed to investigate the role of IUR in PAAD. This study included samples from 58 patients with PAAD and the PAAD cell lines Capan-2 and HPAC. Reverse transcription quantitative PCR was performed to determine gene expression levels. Cell transfections were carried out to assess gene interactions between IUR, miR-34a and CD44. Transwell assays were performed to explore the effects of transfections on cell invasive and migratory abilities. The results demonstrated that IUR was downregulated in PAAD tissue compared with adjacent non-tumor tissue samples and that low expression levels of IUR correlated with poor survival in patients with PAAD. In PAAD tissue samples, the expression of IUR positively correlated with miR-34a expression but negatively correlated with CD44 expression, which is a target of miR-34a. In PAAD cells, overexpression of IUR resulted in miR-34a upregulation and CD44 downregulation. miR-34a overexpression did not affect the expression of IUR but downregulated CD44. In PAAD cells, overexpression of IUR and miR-34a led to decreased invasive and migratory abilities. However, CD44 overexpression played an opposite role and attenuated the effects of IUR and miR-34a overexpression. In conclusion, the results from this study demonstrated that IUR may upregulate miR-34a expression in order to inhibit PAAD cell migration and invasion by downregulating CD44.

SUBMITTER: Li R

PROVIDER: S-EPMC8185698 | biostudies-literature |

REPOSITORIES: biostudies-literature

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LncRNA OIP5-AS1 upregulates snail expression by sponging miR-34a to promote ovarian carcinoma cell invasion and migration.

Project description:BackgroundAlthough OIP5-AS1 has been characterized as an oncogenic lncRNA in many types of cancer, its role and underlying mechanism in ovarian carcinoma (OC) remains unknown. This study aimed to investigate the role of OIP5-AS1 in OC.MethodsOC tissues and non-tumor tissues (ovary tissues within 3 cm around tumors) were collected from 58 OC patients (age range 36 to 67 years old, mean age 51.4 ± 5.9 years old). The expression of OIP5-AS1 and snail in paired tissues were determined by RT-qPCR. The interaction between OIP5-AS1 and miR-34a was predicted by IntaRNA2.0 and confirmed by dual luciferase reporter assay. The effects of overexpression of OIP5-AS1 and miR-34a on the expression of snail were analyzed by RT-qPCR and Western blotting. Cell invasion and migration were analyzed by Transwell assay.ResultsWe observed that the expression of OIP5-AS1 and snail was upregulated and positively correlated with each other in OC. RNA-RNA interaction analysis showed that OIP5-AS1 might sponge miR-34a. In OC cells, overexpression of OIP5-AS1 resulted in the upregulated expression of snail, while overexpression of miR-34a downregulated the expression of snail. In addition, overexpression of miR-34a reduced the effects of overexpression of OIP5-AS1 on the expression of snail. In cell invasion and migration assay, overexpression of OIP5-AS1 and snail resulted in increased OC cell invasion and migration, while overexpression of miR-34a decreased OC cell invasion and migration. Moreover, overexpression of miR-34a attenuated the effects of OIP5-AS1 overexpression on OC cell invasion and migration.ConclusionsTherefore, OIP5-AS1 may upregulate snail expression in OC by sponging miR-34a to promote OC cell invasion and migration.

| S-EPMC7579860 | biostudies-literature

Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a.

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circRNA circ_0055724 Inhibits Trophoblastic Cell Line HTR-8/SVneo's Invasive and Migratory Abilities via the miR-136/N-Cadherin Axis.

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GATA6-AS1 inhibits ovarian cancer cell proliferation and migratory and invasive abilities by sponging miR-19a-5p and upregulating TET2.

Project description:GATA6 antisense RNA 1 (GATA6-AS1) has been reported to be involved in the progression of several types of cancer. In the present study, the role of GATA6-AS1 in ovarian cancer (OC) was explored. Reverse transcription quantitative PCR was used to detect the expression of GATA6-AS1, microRNA (miR)-19a-5p and tet methylcytosine dioxygenase 2 (TET2) in OC and adjacent normal tissues. Furthermore, OC cells with GATA-AS1 either knocked down or overexpressed were established. The Cell Counting Kit-8 assay was used to evaluate cell proliferation and a Transwell assay was used to assess the migratory and invasive abilities of OC cells. A dual luciferase reporter gene assay was used to determine whether GATA6-AS1 and miR-19a-5p, and miR-19a-5p and TET2, may interact with each other. The results demonstrated that GATA6-AS1 expression level was decreased in OC tissues and cells compared with control groups. In addition, GATA6-AS1 overexpression significantly inhibited the proliferation and migratory and invasive abilities of OC cells, whereas GATA6-AS1 downregulation had the opposite effects. Furthermore, GATA6-AS1 adsorbed miR-19a-5p to repress its expression and GTA6-AS1 indirectly upregulated TET2 expression. Taken together, the findings from this study suggested that GATA6-AS1 could inhibit the proliferation and migratory and invasive abilities of OC cells via regulation of the miR-19a-5p/TET2 axis.

| S-EPMC8371982 | biostudies-literature

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma.

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Project description:Background:The mortality and morbidity rates of pancreatic adenocarcinoma have been increasing over the past two decades, and an understanding of the mechanisms underlying pancreatic adenocarcinoma progression is urgently needed. The long non-coding RNA ZFAS1 has been demonstrated to be an oncogene in some cancers, but its function and mechanism in pancreatic adenocarcinoma remain unclear. Methods:The ZFAS1 expression level in pancreatic adenocarcinoma was predicted by bioinformatic analysis, and the expression level of ZFAS1 in pancreatic adenocarcinoma tissue samples and cell lines was further detected by quantitative real-time PCR and in situ hybridization. The functions of ZFAS1 in pancreatic adenocarcinoma in vitro and in vivo were investigated by further bioinformatic analysis. Dual-luciferase reporter assays were used to confirm the binding of ZFAS1/miR-3924 and miR-3924/ROCK2, and rescue assays were performed to further investigate the underlying mechanism. Results:ZFAS1 overexpression in pancreatic adenocarcinoma was predicted and experimentally verified. ZFAS1 silencing inhibited pancreatic adenocarcinoma metastasis in vitro and in vivo. The competing endogenous RNA mechanism of ZFAS1 was also identified. Conclusions:Our results demonstrated the promotive effect of ZFAS1 on pancreatic adenocarcinoma metastasis and suggested its potential role as a novel regulator of ROCK2.

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A rare SNP in pre-miR-34a is associated with increased levels of miR-34a in pancreatic beta cells.

Project description:Changes in the levels of specific microRNAs (miRNAs) can reduce glucose-stimulated insulin secretion and increase beta-cell apoptosis, two causes of islet dysfunction and progression to type 2 diabetes. Studies have shown that single nucleotide polymorphisms (SNPs) within miRNA genes can affect their expression. We sought to determine whether miRNAs, with a known role in beta-cell function, possess SNPs within the pre-miRNA structure which can affect their expression. Using published literature and dbSNP, we aimed to identify miRNAs with a role in beta-cell function that also possess SNPs within the region encoding its pre-miRNA. Following transfection of plasmids, encoding the pre-miRNA and each allele of the SNP, miRNA expression was measured. Two rare SNPs located within the pre-miRNA structure of two miRNA genes important to beta-cell function (miR-34a and miR-96) were identified. Transfection of INS-1 and MIN6 cells with plasmids encoding pre-miR-34a and the minor allele of rs72631823 resulted in significantly (p < 0.05) higher miR-34a expression, compared to cells transfected with plasmids encoding the corresponding major allele. Similarly, higher levels were also observed upon transfection of HeLa cells. Transfection of MIN6 cells with plasmids encoding pre-miR-96 and each allele of rs41274239 resulted in no significant differences in miR-96 expression. A rare SNP in pre-miR-34a is associated with increased levels of mature miR-34a. Given that small changes in miR-34a levels have been shown to cause increased levels of beta-cell apoptosis this finding may be of interest to studies looking at determining the effect of rare variants on type 2 diabetes susceptibility.

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LncRNA SNHG16 contributes to tumor progression via the miR-302b-3p/SLC2A4 axis in pancreatic adenocarcinoma.

Project description:BackgroundIt has been reported that the lncRNA SNHG16 has significantly increased expression in pancreatic adenocarcinoma (PC). However, the functions and mechanisms of SNHG16 are not clear. The aim of this study was to explore the effects of SNHG16 on PC.MethodsqRT-PCR analysis was applied to detect the expression levels of SNHG16, miR-302b-3p and SLC2A4 in PC tissues and cells. CCK8 and EdU assays were used to evaluate the proliferation of PC cells. Transwell assays were used to assess PC cell migration and invasion. Apoptosis was evaluated by flow cytometry, and the expression of apoptosis-related proteins (including Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9) was tested by western blotting. The interactions between miR-302b-3p and SNHG16 or miR-302b-3p and the 3'UTR of SLC2A4 mRNA were clarified by a dual luciferase reporter assay and RNA immunoprecipitation.ResultsSNHG16 expression was significantly elevated in PC tissues and cell lines and was associated with poor prognosis of PC patients. Knockdown of SNHG16 reduced PC cell proliferation, migration and invasion. SNHG16 acted as a sponge to regulate miR-302b-3p expression in PC cells. In addition, miR-302b-3p targeted SLC2A4 directly.ConclusionsSNHG16 promoted the progression of PC via the miR-302b-3p/SLC2A4 axis and was expected to be a potential target for the early diagnosis and treatment of PC.

| S-EPMC7805184 | biostudies-literature

LncRNA FEZF1-AS1 Sponges miR-34a to Upregulate Notch-1 in Glioblastoma.

Project description:Introduction:LncRNA FEZF1-AS1 has been reported to be an oncogene in many types of cancer, while its role in glioblastoma (GBM) is unknown. This study aimed to investigate the potential involvement of FEZF1-AS1 in GBM. Methods:FEZF1-AS1 expression in paired GBM and non-tumor tissues from GBM patients was determined by RT-qPCR. A 2-year follow-up was performed to analyze the prognostic value of FEZF1-AS1 for GBM. Cell transfections were performed to analyze the interactions between FEZF1-AS1, miR-34a and Notch-1. Transwell assay was performed to analyze the role of FEZF1-AS1, miR-34a and Notch-1 in regulating GBM cell invasion and migration. Results:In this study, analysis of TCGA dataset revealed the upregulation of FEZF1-AS1 in GBM, and the overexpression of FEZF1-AS1 in GBM was further confirmed using GBM tissues from GBM patients included in this study. High levels of FEZF1-AS1 were correlated with poor survival. FEZF1-AS1 was predicted to form base pairing with miR-34a. However, overexpression of FEZF1-AS1 and miR-34a failed to affect the expression of each other. However, upregulation of Notch-1, a target of miR-34a, was observed after FEZF1-AS1 in GBM cells. Moreover, increased invasion and migration rates of GBM cells were observed after FEZF1-AS1 and Notch-1 overexpression. MiR-34a played an opposite role and reduced the effects of FEZF1-AS1 and Notch-1 overexpression. Conclusion:FEZF1-AS1 may sponge miR-34a to upregulate Notch-1 in GBM, thereby promoting cancer cell invasion and migration.

| S-EPMC7075242 | biostudies-literature

MiR-34a regulates the invasive capacity of canine osteosarcoma cell lines.

Project description:BackgroundOsteosarcoma (OSA) is the most common bone tumor in children and dogs; however, no substantial improvement in clinical outcome has occurred in either species over the past 30 years. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a fundamental role in cancer. The purpose of this study was to investigate the potential contribution of miR-34a loss to the biology of canine OSA, a well-established spontaneous model of the human disease.Methodology and principal findingsRT-qPCR demonstrated that miR-34a expression levels were significantly reduced in primary canine OSA tumors and canine OSA cell lines as compared to normal canine osteoblasts. In canine OSA cell lines stably transduced with empty vector or pre-miR-34a lentiviral constructs, overexpression of miR-34a inhibited cellular invasion and migration but had no effect on cell proliferation or cell cycle distribution. Transcriptional profiling of canine OSA8 cells possessing enforced miR-34a expression demonstrated dysregulation of numerous genes, including significant down-regulation of multiple putative targets of miR-34a. Moreover, gene ontology analysis of down-regulated miR-34a target genes showed enrichment of several biological processes related to cell invasion and motility. Lastly, we validated changes in miR-34a putative target gene expression, including decreased expression of KLF4, SEM3A, and VEGFA transcripts in canine OSA cells overexpressing miR-34a and identified KLF4 and VEGFA as direct target genes of miR-34a. Concordant with these data, primary canine OSA tumor tissues demonstrated increased expression levels of putative miR-34a target genes.ConclusionsThese data demonstrate that miR-34a contributes to invasion and migration in canine OSA cells and suggest that loss of miR-34a may promote a pattern of gene expression contributing to the metastatic phenotype in canine OSA.

| S-EPMC5749745 | biostudies-literature

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