Noncoding RNAs in osteosarcoma: Implications for drug resistance

Lin, Zhengjun; Xie, Xubin; Lu, Shijuan

doi:10.1016/j.canlet.2021.02.007

Cited by 23 publications

(20 citation statements)

References 103 publications

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“… 7 , 8 Endogenous or acquired drug resistance is one of the important causes of treatment failure and poor prognosis in patients with osteosarcoma. 9 Osteosarcoma is one of the most heterogeneous solid tumors, 10 and different patients with osteosarcoma have obvious differences in the efficacy of preoperative chemotherapy. At present, tumor cell necrosis rate of more than 90% is considered as effective chemotherapy, while tumor cell necrosis rate of less than 90% is considered as unsatisfactory chemotherapy efficacy, and endogenous drug resistance may exist.…”

Section: Introductionmentioning

confidence: 99%

Development of a Nomogram for Predicting the Efficacy of Preoperative Chemotherapy in Osteosarcoma

Huang¹,

Chen²,

Lou³

et al. 2021

IJGM

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Background Due to the obvious heterogeneity of osteosarcoma, many patients are not sensitive to neoadjuvant chemotherapy. In this study, the clinical characteristics and auxiliary examinations of patients with osteosarcoma were used to predict the effect of preoperative chemotherapy, so as to guide the clinical adjustment of the treatment plan to improve the prognosis of patients. Methods In this study, 90 patients with pathologically confirmed osteosarcoma were included, and they were randomly divided into training cohort (n=45) and validation cohort (n=45). A prediction model of preoperative chemotherapy efficacy for osteosarcoma was established by multivariate logistic regression analysis, and a nomogram was used as the visualization of the model. The ROC curve and C-index were used to evaluate the accuracy of the nomogram. Decision curve analysis (DCA) was used to evaluate the net benefit of the nomogram in predicting the efficacy of neoadjuvant chemotherapy under different threshold probabilities. Results In the study, the age, gender, location, tumor volume, metastasis at the first visit, MSTS staging, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were used in the multivariate logistic regression analysis and the construction of the nomogram. The AUC and C-index of the training cohort were 0.793 (95% CI: 0.632, 0.954) and 0.881 (95% CI: 0.776, 0.986), respectively. The AUC and C-index in the validation cohort were 0.791 (95% CI: 0.644, 0.938) and 0.813 (95% CI: 0.679, 0.947), respectively, which were close to the training cohort. DCA showed that the model had good clinical application value. Conclusion Based on the clinical characteristics of patients and auxiliary examinations, the nomogram can be good used to predict the efficacy of preoperative chemotherapy for osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Development of a Nomogram for Predicting the Efficacy of Preoperative Chemotherapy in Osteosarcoma

Huang¹,

Chen²,

Lou³

et al. 2021

IJGM

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“…Circular RNAs (circRNAs), a type of non-coding RNAs, have been found aberrantly expressed in multiple diseases and play a pivotal role in cancer initiation, progression, and immune response ( 12 ). Of note, accumulating evidence has unraveled that circRNAs participated in multiple aspects of osteosarcoma development, such as osteosarcoma cell metastasis ( 13 ), drug resistance ( 14 ), and in vivo tumorigenesis ( 12 ), on the basis of their biological functions as miRNA sponge, gene regulators at posttranscriptional levels, and also interactors with proteins ( 15 , 16 ). Further, circNRIP1 (also known as hsa_circ_0004771) has been documented to be a novel diagnostic biomarker and an oncogenic circRNA for malignant development in several cancers, including gastric cancer and colorectal cancer due to its differential expression in these cancers ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis

2021

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Emerging evidence indicates that extracellular vesicle (EV)-encapsulated circRNAs have the potential diagnostic and prognostic values for malignancies. However, the role of circNRIP1 in osteosarcoma remains unclear. We herein investigated the therapeutic potential of circNRIP1 delivered by bone marrow mesenchymal stem cell–derived EVs (BMSC-EVs) in osteosarcoma. The expression of circNRIP1 was examined in the clinical tissue samples of osteosarcoma patients, after which the downstream genes of circNRIP1 were bioinformatically predicted. Gain- and loss-of function assays were then performed in osteosarcoma cells with manipulation of circNRIP1 and miR-532-3p expression. EVs isolated from BMSCs were characterized and co-cultured with osteosarcoma cells to examine their effects on cell phenotypes, as reflected by CCK-8 and Transwell assays. Further, a mouse model of tumor xenografts was established for in vivo substantiation. circNRIP1 was upregulated in osteosarcoma tissues and cells. Overexpression of circNRIP1 promoted the proliferative, migratory, and invasive potential of osteosarcoma cells. Co-culture data showed that BMSC-EVs could transfer circNRIP1 into osteosarcoma cells where it competitively bound to miR-532-3p and weakened miR-532-3p’s binding ability to AKT3. By this mechanism, the PI3K/AKT signaling pathway was activated and the malignant characteristics of osteosarcoma cells were stimulated. In vivo experimental results unveiled that circNRIP1-overexpressing BMSC-EVs in nude mice resulted in enhanced tumor growth. In conclusion, the BMSC-EV-enclosed circNRIP1 revealed a new molecular mechanism in the pathogenesis of osteosarcoma, which might provide a novel therapeutic target for osteosarcoma.

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“…In recent years, with the rapid development of bioinformatic analysis and RNA sequencing technologies, the crucial regulatory role of circRNAs has been explored in a series of tumors. [22][23][24] Chen et al found that circCAMSAP1 expression markedly increased within human OSA cells and tissue, which was closely related to OSA progression. 25 More recently, Qiu et al 26 established a circRNA-miRNA-mRNA network in OSA, in which four mRNAs were suggested as the overall survival-related mRNAs according to survival analysis.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

Gu¹,

Duan²,

Liu³

et al. 2021

CMAR

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Introduction Osteosarcoma (OSA) is characterized by its relatively high morbidity in children and adolescents. Patients usually have advanced disease at the time of diagnosis, resulting in poor outcomes. This study focused on building a circular RNA-based ceRNA network to develop a reliable model for OSA risk prediction. Methods We used the Gene Expression Omnibus (GEO) datasets to explore the expression patterns of circRNA, miRNA, and mRNA in OSA. The prognostic value of circRNA host genes was assessed with data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database using Kaplan–Meier survival analysis. We established a circRNA-related ceRNA network and annotated its biological functions. Next, we developed a prognostic risk signature based on mRNAs extracted from the ceRNA network. We also developed a prognostic model and constructed a nomogram to enhance the prediction of OSA prognosis. Results We identified 166 DEcircRNAs, 233 DEmiRNAs, and 1317 DEmRNAs and used them to create a circRNA-related ceRNA network. We then established a prognostic risk model consisting of four genes (MLLT11, TNFRSF11B, SLC7A7, and PARVA). Moreover, we found that inhibition of MLLT11 and SLC7A7 blocked OSA cell proliferation and migration in in vitro experiments. Conclusion Our study identifies crucial prognostic genes and provides a circRNA-related ceRNA network for OSA, which will contribute to the elucidation of the molecular mechanisms underlying the oncogenesis and development of OSA.

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Noncoding RNAs in osteosarcoma: Implications for drug resistance

Cited by 23 publications

References 103 publications

Development of a Nomogram for Predicting the Efficacy of Preoperative Chemotherapy in Osteosarcoma

Development of a Nomogram for Predicting the Efficacy of Preoperative Chemotherapy in Osteosarcoma

CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis

Circular RNA-Related CeRNA Network and Prognostic Signature for Patients with Osteosarcoma

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