Long noncoding <scp>RNA PWRN1</scp> is lowly expressed in osteosarcoma and modulates cancer proliferation and migration by targeting <scp>hsa‐miR</scp>‐214‐5p

Lin

et al. 2023

PeerJ

Background Long noncoding RNAs (lncRNAs) have been shown to be involved in the regulation of numerous biological processes in embryonic development. We aimed to explore lncRNA expression profiles in ventricular septal defects (VSDs) and reveal their potential roles in heart development. Methods Microarray analyses were performed to screen differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) in the amniotic fluid between the VSD group and the control group. Bioinformatics analyses were further used to identify the functional enrichment and signaling pathways of important mRNAs. Then, a coding–noncoding gene coexpression (CNC) network and competitive endogenous RNAs (ceRNA) network were drawn. Finally, qRT‒PCR was performed to verify several hub lncRNAs and mRNAs in the network. Results A total of 710 DE-lncRNAs and 397 DE-mRNAs were identified in the VSD group. GO and KEGG analyses revealed that the DE-mRNAs were enriched in cardiac development-related biological processes and pathways, including cell proliferation, cell apoptosis, and the Sonic Hedgehog signaling pathway. Four VSD related mRNAs was used to construct the CNC network, which included 149 pairs of coexpressing lncRNAs and mRNAs. In addition, a ceRNA network, including 15 lncRNAs, 194 miRNAs, and four mRNAs, was constructed to reveal the potential regulatory relationship between lncRNAs and protein-coding genes. Finally, seven RNAs in the ceRNA network were validated, including IDS, NR2F2, GPC3, LINC00598, GATA3-AS1, PWRN1, and LINC01551. Conclusion Our study identified some lncRNAs and mRNAs may be potential biomarkers and therapeutic targets for foetuses with VSD, and described the lncRNA-associated ceRNA network in the progression of VSD.

Section: Discussionmentioning

confidence: 99%

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects

Lin

et al. 2023

PeerJ

“…A distinctly downregulated lncRNA, Prader-Willi Region Non-Protein Coding RNA (PWRN1), was discovered during a study carried out by Shi et al and was found to be significantly correlated with advanced-stage metastasis, low survival rates in cancer patients, and chemoresistance. One of the major findings in this study was that cancer patients with low PWRN1 expression had much worse OS than those with high PWRN1 [ 62 ]. Additionally, when PWRN1 lncRNA was overexpressed in OS cell lines, the amount of cancer cell proliferation was drastically suppressed, and chemoresistance to cisplatin was markedly reduced.…”

Section: Non-coding Rnamentioning

confidence: 99%

“…Overexpression was also shown to suppress the in vivo growth of OS xenotransplants. Notably, miR-214-5p (a human microRNA) was identified as a possible ceRNA candidate for PWRN1, and the overexpression of miR-214-5p reversed the anti-cancer effects of PWRN1 on OS cell proliferation and chemoresistance [ 62 ].…”

Section: Non-coding Rnamentioning

confidence: 99%

Epigenetic Changes Associated with Osteosarcoma: A Comprehensive Review

Twenhafel,

Moreno,

Punt

et al. 2023

Cells

Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. While clinical outcomes have improved, the 5-year survival rate is only around 60% if discovered early and can require debilitating treatments, such as amputations. A better understanding of the disease could lead to better clinical outcomes for patients with osteosarcoma. One promising avenue of osteosarcoma research is in the field of epigenetics. This research investigates changes in genetic expression that occur above the genome rather than in the genetic code itself. The epigenetics of osteosarcoma is an active area of research that is still not fully understood. In a narrative review, we examine recent advances in the epigenetics of osteosarcoma by reporting biomarkers of DNA methylation, histone modifications, and non-coding RNA associated with disease progression. We also show how cancer tumor epigenetic profiles are being used to predict and improve patient outcomes. The papers in this review cover a large range of epigenetic target genes and pathways that modulate many aspects of osteosarcoma, including but not limited to metastases and chemotherapy resistance. Ultimately, this review will shed light on the recent advances in the epigenetics of osteosarcoma and illustrate the clinical benefits of this field of research.

“…Zhu et al demonstrated that the overexpression of miR‐142/miR‐22 reversed doxorubicin chemoresistance of osteosarcoma by inhibiting autophagy 6 . Shi et al revealed the miR‐214‐5p conferred cisplatin resistance in osteosarcoma 7 . miR‐519d‐3p (miR‐519d) is universally expressed in various cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐519d‐3p antagonizes osteosarcoma resistance against cisplatin by targeting PD‐L1

Molecular Carcinogenesis

Zhenjun

Qiu

et al. 2021

Accumulating evidence indicates that a ligand of programmed cell death receptor‐1 (PD‐L1) participates in the progression and recurrence of multiple malignancies, including osteosarcoma. Nevertheless, the role of PD‐L1 in chemoresistance development is not fully understood. In the current study, we aim to clarify the interaction of miR‐519d‐3p and PD‐L1 in the development of cisplatin resistance. Immunohistochemistry, quantitative reverse‐transcription polymerase reaction, and Western blot were used to evaluate PD‐L1 expression. MTT and transwell migration assays were used to measure cell growth and motility, respectively. ENCORI, miRCode, and miRDB databases were recruited to predict candidate miRNAs targeting PD‐L1. The binding sequences of miR‐519d‐3p and PD‐L1 3ʹ untranslated region were identified by dual‐luciferase reporter and RNA immunoprecipitation assays. Flow cytometric analysis was conducted to measure the cycle distribution and cell apoptosis. Metastatic mouse models were generated with cisplatin‐resistant sublines by intravenous injection. We found that PD‐L1 expression was positively correlated to cisplatin resistance and metastasis, whereas miR‐519d‐3p expression was reduced in cisplatin‐resistant specimens and was negatively correlated to cisplatin resistance and metastasis of osteosarcoma. We demonstrated that miR‐519d‐3p overexpression reversed cisplatin resistance, induced G1/S phase arrest and apoptosis. In addition, we proved that miR‐519d‐3p inhibited lung metastasis by establishing cisplatin‐resistant MG63 metastatic xenograft models. The present findings suggest that miR‐519d‐3p/PD‐L1 axis is a novel signaling pathway contributing to cisplatin resistance. Our study provides new clues for curing refractory osteosarcoma beyond immune checkpoint inhibitors.