Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis

Guan, Huapeng; Xu, Hao; Chen, Jinshui; Wu, Weishan; Chen, Dongfeng; Chen, Yungang; Sun, Jianzhong

doi:10.1186/s12935-021-02016-5

Cited by 11 publications

(9 citation statements)

References 33 publications

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“…Gao et al confirmed that suppression of circ_0084582 restrained the malignant phenotypes of OS cells via sponging miR-485-3p and thereby regulating JAG1 expression [7]. In another study, Guan et al found that highly expressed circ_0001721 contributed to TCF4 expression, cell growth and metastasis in doxorubicin-resistant OS cells by targeting miR-758 [9]. Although studies have confirmed that high level of circ-NT5C2 appeared in OS tumor tissues through RNA sequencing, there was no research on the specific role and mechanism of circ-NT5C2 in the pathogenesis of OS [20].…”

Section: Discussionmentioning

confidence: 92%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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Background Circ-NT5C2 has been confirmed to be highly expressed and associated to the progression of osteosarcoma (OS). However, the behind mechanism of circ-NT5C2 involvement in OS remains unclear. Methods The expression of circ-NT5C2, miR-488-3p and FZD4 was measured by quantitative real-time PCR, and the protein expression of E-cadherin, N-cadherin and FZD4 was detected by western blot. Cell counting kit 8 assay, colony formation assay and 5-ethynyl-2-deoxyuridine assay were performed to assess the cell proliferation. The cell apoptosis was measured by flow cytometry and Caspase3/Caspase9 Activity Assay Kits. Cell migration and invasion were detected by transwell assay. Dual-luciferase reporter assay and RIP assay were carried out to determine the binding relation among circ-NT5C2, miR-488-3p and FZD4. Animal experiment and immunohistochemistry analysis were conducted to explore the role of circ-NT5C2 in tumor growth in vivo. Results Comparing with controls, the expression of circ-NT5C2 and FZD4 was upregulated and miR-488-3p expression was downregulated in OS tumor tissues and cells. Circ-NT5C2 overexpression facilitated the cell proliferation and motility and induced cell apoptosis of OS cells, whereas circ-NT5C2 knockdown had the opposite effect. Besides, we also found and confirmed that circ-NT5C2 regulated cell malignant behaviors via modulating miR-488-3p/FZD4 axis in OS. Moreover, circ-NT5C2 silencing repressed the growth of xenografts in vivo. Conclusion Circ-NT5C2 upregulated FZD4 expression via sponging miR-488-3p, thus facilitating cell malignant behaviors in OS.

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Section: Discussionmentioning

confidence: 92%

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

et al. 2022

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“…The DOX resistance in osteosarcoma can be mediated by TCF4 overexpression. In this case, circ‐0001721 promotes TCF4 expression via miRNA‐758 downregulation to induce DOX resistance 94 . Another experiment reveals that circATXN7 increases HOXA11 expression via miRNA‐149‐5p downregulation to increase breast cancer progression and to inhibit DOX resistance 97 .…”

Section: Doxorubicin: Mechanism Of Action and Resistancementioning

confidence: 98%

“…In this case, circ-0001721 promotes TCF4 expression via miRNA-758 downregulation to induce DOX resistance. 94 Another experiment reveals that circATXN7 increases HOXA11 expression via miRNA-149-5p downregulation to increase breast cancer progression and to inhibit DOX resistance. 97 Furthermore, EMT is responsible for cancer metastasis 98 The CS is a pH-sensitive agent due to the presence of amine groups ( NH 2 ) that undergoes protonation in acidic pH 108,109 ; higher pH significantly decreases the solubility of CS.…”

Section: Doxorubicin: Mechanism Of Action and Resistancementioning

confidence: 99%

Chitosan‐based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy

Ashrafizadeh

Hushmandi

Mirzaei

et al. 2022

Bioengineering & Transla Med

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Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS‐based nanoparticles (CS‐NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS‐NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance. These nanoarchitectures can provide co‐delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co‐loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid‐, carbon‐, polymeric‐ and metal‐based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS‐NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS‐NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH‐sensitive release of DOX can occur. Furthermore, redox‐ and light‐responsive CS‐NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS‐NPs, we expect to soon see significant progress towards clinical translation.

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“…DOX resistance of osteosarcoma is facilitated by hsa_circ_0004674 through the Wnt/b-catenin pathway via modulation of the miR-342-3p/FBN1 axis (106). Moreover, some circRNAs potentiate DOX resistance and facilitate the progression of osteosarcomas, such as circ_0001721, circSAMD4A, circ_0002060, and circ_0003496 (20,(107)(108)(109). Zhu et al report that resistance to DOX and CDDP can be weakened by suppressing circPVT1 expression in osteosarcoma cells (21).…”

Section: Circrnas and Osteosarcoma Drug Resistancementioning

confidence: 99%

The Role of Circular RNAs in the Drug Resistance of Cancers

et al. 2022

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Cancer is a major threat to human health and longevity. Chemotherapy is an effective approach to inhibit cancer cell proliferation, but a growing number of cancer patients are prone to develop resistance to various chemotherapeutics, including platinum, paclitaxel, adriamycin, and 5-fluorouracil, among others. Significant progress has been made in the research and development of chemotherapeutic drugs over the last few decades, including targeted therapy drugs and immune checkpoint inhibitors; however, drug resistance still severely limits the application and efficacy of these drugs in cancer treatment. Recently, emerging studies have emphasized the role of circular RNAs (circRNAs) in the proliferation, migration, invasion, and especially chemoresistance of cancer cells by regulating the expression of related miRNAs and targeted genes. In this review, we comprehensively summarized the potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair, among others. Furthermore, we highlighted the potential value of circRNAs as new therapeutic targets and prognostic biomarkers for cancer.

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Circ_0001721 enhances doxorubicin resistance and promotes tumorigenesis in osteosarcoma through miR-758/TCF4 axis

Cited by 11 publications

References 33 publications

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

Circ-NT5C2 stimulates FZD4 expression to promote the malignant progression of osteosarcoma by targeting miR-488-3p

Chitosan‐based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy

The Role of Circular RNAs in the Drug Resistance of Cancers

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