MiR-197-3p promotes osteosarcoma stemness and chemo-resistance by inhibiting SPOPL
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA928683 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:First-line treatment for osteosarcoma includes chemotherapy and surgery. However, the five-year survival rate of refractory osteosarcoma remains unsatisfactory. Osteosarcoma cancer stem cells, possessing stemness and chemoresistance, are one of the critical causes for poor response to chemotherapy. Elucidating regulatory signaling pathways of osteosarcoma cancer stem cells may provide a rationale for improving regimens against chemoresistant osteosarcoma. Methotrexate (MTX)-resistant osteosarcoma cells were established. microRNA expression profiles were used for detecting differentially expressed microRNA in resistant clones and the parental cells. microRNA target databases were employed to predict potential microRNA and mRNA interaction. Flow cytometry was performed to measure stem cell marker Prominin-1 (CD133) positive cells. Im-munofluorescence staining was applied to detect CD133 expression. miR-197-3p mimic or an-ti-miR-197-3p stably transfected cells were used to generate xenograft models. In the study, we found miR-197-3p was increased in MTX-resistant cell lines. Overexpression of miR-197-3p en-hanced the expression of cancer stem cell markers CD133, Octamer-binding protein 4 (OCT4), Transcription factor SOX-2 (SOX2), and Homeobox protein NANOG (NANOG), as well as chemoresistance-associated genes ATP-dependent translocase ABCB1 (ABCB1) and Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2), whereas miR-197-3p knockdown inhibited stemness and recovered sensitivity to MTX. We also classified the tumor suppressor Speckle-type POZ protein-like (SPOPL) as a target of miR-197-3p. The miR-197-3p mutation that cannot combine SPOPL promoter regions was unable to sustain stemness or chemoresistance. Collectively, we discovered miR-197-3p conferred osteosarcoma stemness and chemotherapy resistance by targeting SPOPL, prompting promising therapeutic candidates for refractory oste-osarcoma treatment. miRNA qPCR assay
2023-01-31 | GSE223857 | GEO
Project description:First-line treatment for osteosarcoma includes chemotherapy and surgery. However, the five-year survival rate of refractory osteosarcoma remains unsatisfactory. Osteosarcoma cancer stem cells, possessing stemness and chemoresistance, are one of the critical causes of poor response to chemotherapy. Elucidating regulatory signaling pathways of osteosarcoma cancer stem cells may provide a rationale for improving regimens against chemoresistant osteosarcoma. Methotrexate (MTX)-resistant osteosarcoma cells were established. microRNA expression profiles were used for detecting differentially expressed microRNA in resistant clones and the parental cells. microRNA target databases were employed to predict potential microRNA and mRNA interactions. Flow cytometry was performed to measure stem cell marker Prominin-1 (CD133)-positive cells. Immunofluorescence staining was applied to detect CD133 expression. miR-197-3p mimic or anti-miR-197-3p stably transfected cells were used to generate xenograft models. In the study, we found that miR-197-3p was increased in MTX-resistant cell lines. Overexpression of miR-197-3p enhanced the expression of cancer stem cell markers CD133, Octamer-binding protein 4 (OCT4), Transcription factor SOX-2 (SOX2), and Homeobox protein NANOG (NANOG), as well as chemoresistance-associated genes ATP-dependent translocase ABCB1 (ABCB1) and Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2), whereas miR-197-3p knockdown inhibited stemness and recovered sensitivity to MTX. We also classified the tumor suppressor Speckle-type POZ protein-like (SPOPL) as a target of miR-197-3p. The miR-197-3p mutation that could not combine SPOPL promoter regions was unable to sustain stemness or chemoresistance. Collectively, we discovered miR-197-3p conferred osteosarcoma stemness and chemotherapy resistance by targeting SPOPL, prompting promising therapeutic candidates for refractory osteosarcoma treatment.
| S-EPMC9917813 | biostudies-literature
Project description:Background: Psoriasis is a chronic inflammatory disorder with cutaneous and systemic manifestations and substantial negative effects on patients' life quality. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Evidence suggests that miRNAs play a role in the pathogenesis of psoriasis. Previously studies, from others and by us, show-specific miRNAs that are differentially expressed between the psoriasis lesion and healthy skin. One of those miRNAs is miR-197-3p whose expression is down-regulated in the psoriatic lesions compared to normal or uninvolved psoriatic skin. In order to understand miR-197's role in psoriasis, we found that it could modulate IL-22 and IL-17 signaling. Objectives: We aimed to identify additional biochemical targets of miR-197 in psoriasis. Methods: We have chosen to apply a transcriptome-wide biochemical approach (PAR-CLIP) to search for new targets of miR-197 in keratinocytes. Results: in this work, using PAR-CLIP, we found an additional biochemical target of miR-197, one of the subunits of the receptor to IL-6. IL-6R is known to be up-regulated in psoriasis and even was considered as a possible therapeutic target. Conclusions: From the present data and our previous studies it appears that miR-197 is a major regulator of the interaction between immune system cells and keratinocytes.
2020-08-25 | GSE155538 | GEO
Project description:Bibersteinia trehalosi strain:SKBRP 197 | isolate:SKBRP 197 Genome sequencing
| PRJNA1075736 | ENA
Project description:In general, microRNAs (miRNAs) regulate gene expression by repressing translation or promoting the degradation of their target genes. To strategically identify direct microR-197 (miR-197) target genes, we first performed mRNA microarray analyses of A549, PC14, and PC14CDDP cells that were transiently transfected with either pre-miR-197 or LNA-miR-197 and their controls. We observed that 1037 predicted target genes exhibited expression alterations consistently across the three different lung cancer cell lines.
2017-02-09 | GSE56266 | GEO
Project description:Sinorhizobium fredii USDA 197 genome sequencing
| PRJNA1115329 | ENA
Project description:Osteosarcoma (OS) is one of the most common malignant bone tumours and generally occurs in children and adolescents. Increasing evidence has demonstrated that dysregulated long non‑coding RNAs (lncRNAs) play crucial roles in the progression of various human neoplasms. Among these, tumour suppressor candidate 8 (TUSC8) is a novel lncRNA and has been reported to function as a tumour suppressor in cervical cancer. However, the exact role of TUSC8 in OS remains largely unknown. In the present study, it was observed that TUSC8 was markedly downregulated in OS tissues and cell lines. Functional experiments demonstrated that the overexpression of TUSC8 significantly suppressed the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT), whereas it accelerated the apoptosis of OS cells. Mechanistically, TUSC8 served as a sponge for miR‑197‑3p, and EH‑domain containing 2 (EHD2) was identified as a downstream target molecule of miR‑197‑3p. Further investigations indicated that EHD2 knockdown significantly reversed the effects on OS cellular processes induced by TUSC8 overexpression. On the whole, these findings indicate that TUSC8 functions as a competing endogenous RNA (ceRNA) to suppress OS cell growth and EMT via the miR‑197‑3p/EHD2 axis. TUSC8 may thus function as a potential therapeutic target in OS treatment.
| S-EPMC7447318 | biostudies-literature
Project description:Citrobacter freundii SBS 197 Genome sequencing
| PRJNA228973 | ENA
Project description:Background: Osteosarcomas are the most common primary malignant tumors of bone and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs capable of regulating gene expression at the post transcriptional level, and miRNAs and their target genes may represent novel therapeutic targets or biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in osteosarcoma development, global microarray analyses of a panel of 19 human osteosarcoma cell lines was performed. Principal findings: We identified 177 miRNAs that were differentially expressed in osteosarcoma cell lines relative to normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486-5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497, and miR-206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines. All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29, miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/the p85M-NM-1 regulatory subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b, miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR-497 was identified with an intermediate expression level in osteosarcoma clinical samples compared to osteoblasts and bone, which may reflect the differentiation level of osteosarcoma relative to the undifferentiated osteoblast and fully differentiated normal bone. Significance: This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex genetic mechanisms of osteosarcoma development and progression. 19 osteosarcoma cell lines, 4 normal bones used as controls. No replicates. The group of osteosarcomas are compared to the group of normal bones.
2012-10-16 | E-GEOD-28424 | biostudies-arrayexpress
Project description:Background: Osteosarcomas are the most common primary malignant tumors of bone and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs capable of regulating gene expression at the post transcriptional level, and miRNAs and their target genes may represent novel therapeutic targets or biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in osteosarcoma development, global microarray analyses of a panel of 19 human osteosarcoma cell lines was performed. Principal findings: We identified 177 miRNAs that were differentially expressed in osteosarcoma cell lines relative to normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486-5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497, and miR-206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines. All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29, miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/the p85α regulatory subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b, miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR-497 was identified with an intermediate expression level in osteosarcoma clinical samples compared to osteoblasts and bone, which may reflect the differentiation level of osteosarcoma relative to the undifferentiated osteoblast and fully differentiated normal bone. Significance: This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex genetic mechanisms of osteosarcoma development and progression. 19 osteosarcoma cell lines, 4 normal bones used as controls. No replicates. The group of osteosarcomas are compared to the group of normal bones.
2012-10-16 | E-GEOD-28423 | biostudies-arrayexpress