Silencing of circCYP51A1 represses cell progression and glycolysis by regulating miR-490-3p/KLF12 axis in osteosarcoma under hypoxia

Jiao, Yang; Liu, Zhiwei; Liu, Ben; Sun, Lijun

doi:10.1016/j.jbo.2022.100455

Cited by 5 publications

(3 citation statements)

References 41 publications

(39 reference statements)

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“…A normal osteoblastic cell line hFOB 1.19 and four human OS cell lines (U2OS, Soas2, 143B, and MG63) obtained from the ATCC (Manassas) were cultured in DMEM (Gibco) containing 10% FBS (PM150210B; Procell) with 5% CO 2 at 37°C. To establish a hypoxic condition, U2OS and Soas2 cells were cultured in an incubator with 1% O 2 /5% CO 2 /94% N 2 as previously described 22 …”

Section: Methodsmentioning

confidence: 99%

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The knockdown of lncRNA DLGAP1‐AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR‐451a/HK2 axis

Zheng,

Li,

Zheng

et al. 2023

Cancer Science

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Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1‐AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT‐qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1‐AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial–mesenchymal transition (EMT)‐related markers. The proliferation of OS cells was determined using a CCK‐8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR‐451a, HK2, and DLGAP1‐AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1‐AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1‐AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1‐AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1‐AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1‐AS2 overexpression accelerated the progression of OS. We further found that DLGAP1‐AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1‐AS2 bound to miR‐451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1‐AS2/miR‐451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1‐AS2 upregulated HK2 expression by sponging miR‐451a to accelerate OS development.

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Section: Methodsmentioning

confidence: 99%

“…To establish a hypoxic condition, U2OS and Soas2 cells were cultured in an incubator with 1% O 2 /5% CO 2 /94% N 2 as previously described. 22 …”

Section: Methodsmentioning

confidence: 99%

The knockdown of lncRNA DLGAP1‐AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR‐451a/HK2 axis

Zheng,

Li,

Zheng

et al. 2023

Cancer Science

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“…Moreover, the circCYP51A1, that was upregulated under hypoxia conditions, can markedly induce the lactate production and glucose consumption by sponging miR-490-3p and regulating KLF12. Interestingly, the knockdown of circCYP51A1 in xenograft mice models can reduce tumor growth by downregulating KLF12 and consequently reducing glycolysis associated markers, such as GLUT1, HK2 and LDHA [ 264 ].…”

Section: Cernets Involving Circrnasmentioning

confidence: 99%

Osteosarcoma in a ceRNET perspective

Mosca,

Alessio,

Di Paola

et al. 2024

J Biomed Sci

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Osteosarcoma (OS) is the most prevalent and fatal type of bone tumor. It is characterized by great heterogeneity of genomic aberrations, mutated genes, and cell types contribution, making therapy and patients management particularly challenging. A unifying picture of molecular mechanisms underlying the disease could help to transform those challenges into opportunities.This review deeply explores the occurrence in OS of large-scale RNA regulatory networks, denominated “competing endogenous RNA network” (ceRNET), wherein different RNA biotypes, such as long non-coding RNAs, circular RNAs and mRNAs can functionally interact each other by competitively binding to shared microRNAs. Here, we discuss how the unbalancing of any network component can derail the entire circuit, driving OS onset and progression by impacting on cell proliferation, migration, invasion, tumor growth and metastasis, and even chemotherapeutic resistance, as distilled from many studies. Intriguingly, the aberrant expression of the networks components in OS cells can be triggered also by the surroundings, through cytokines and vesicles, with their bioactive cargo of proteins and non-coding RNAs, highlighting the relevance of tumor microenvironment. A comprehensive picture of RNA regulatory networks underlying OS could pave the way for the development of innovative RNA-targeted and RNA-based therapies and new diagnostic tools, also in the perspective of precision oncology.

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Non-coding RNAs in metabolic reprogramming of bone and soft tissue sarcoma: Fundamental mechanism and clinical implication

Chen¹,

Hao²,

Zhang³

et al. 2023

Biomedicine & Pharmacotherapy

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Silencing of circCYP51A1 represses cell progression and glycolysis by regulating miR-490-3p/KLF12 axis in osteosarcoma under hypoxia

Cited by 5 publications

References 41 publications

The knockdown of lncRNA DLGAP1‐AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR‐451a/HK2 axis

The knockdown of lncRNA DLGAP1‐AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR‐451a/HK2 axis

Osteosarcoma in a ceRNET perspective

Non-coding RNAs in metabolic reprogramming of bone and soft tissue sarcoma: Fundamental mechanism and clinical implication

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