Synergistic Autophagy Effect of miR-212-3p in Zoledronic Acid-Treated In Vitro and Orthotopic In Vivo Models and in Patient-Derived Osteosarcoma Cells

Oh, Ju Yeon; Kim, Eun Ho; Lee, Yeon‐Joo; Sai, Sei; Lim, Sun Ha; Park, Jang Woo; Chung, Hye Kyung; Kim, Joon; Varès, Guillaume; Takahashi, Akio; Jeong, Youn Kyoung; Kim, Mi Sook; Kong, Chang Bae

doi:10.3390/cancers11111812

Cited by 12 publications

(10 citation statements)

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“…Among these predicted miRNAs that potentially pair to circNFIX, miR-212-3p was a strong candidate in the current work owing to its anti-tumor role in a variety of human malignancies, such as ovarian cancer, glioma and osteosarcoma. [30][31][32] Moreover, miR-212-3p restrained the tumorigenesis of gastric cancer and bladder cancer by inhibiting the expression of a target, such as SRY-box transcription factor 6 (Sox6) and nuclear factor IA (NFIA). 33,34 A previous document demonstrated the tumor suppressive impact of miR-212-3p in NSCLC malignant progression.…”

Section: Discussionmentioning

confidence: 99%

<p>CircNFIX Acts as a miR-212-3p Sponge to Enhance the Malignant Progression of Non-Small Cell Lung Cancer by Up-Regulating ADAM10</p>

Lü¹,

Zhu²,

Qin³

et al. 2020

CMAR

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Background: Non-small cell lung cancer (NSCLC) remains the most commonly diagnosed malignancy and the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have been demonstrated to play critical roles in human carcinogenesis, including NSCLC. However, it is still unclear whether circRNA nuclear factor I X (circNFIX) is implicated in the molecular pathogenesis of NSCLC. Methods: The expression levels of circNFIX, miR-212-3p and a disintegrin and metalloproteinases 10 (ADAM10) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell viability was gauged by the Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were determined by transwell assays. Glucose uptake and lactate product were determined using the assay kits. Targeted relationships among circNFIX, miR-212-3p and ADAM10 were verified by dual-luciferase reporter and RNA pulldown assays. Additionally, the xenograft model assays were carried out to analyze the role of circNFIX in tumor growth in vivo. Results: Our data revealed that circNFIX was overexpressed in NSCLC and predicted poor prognosis of NSCLC patients. CircNFIX knockdown suppressed NSCLC cell viability, migration, invasion and glycolysis in vitro and hampered tumor growth in vivo. Mechanistically, CircNFIX acted as a molecular sponge of miR-212-3p, and the repressive effect of circNFIX knockdown on NSCLC cell malignant progression was mediated by miR-212-3p. Moreover, ADAM10 was a direct target of miR-212-3p, and circNFIX influenced ADAM10 expression by sponging miR-212-3p in NSCLC cells. Furthermore, the silencing of ADAM10 hindered NSCLC cell viability, migration, invasion and glycolysis in vitro. Conclusion: Our findings first identified that the knockdown of circNFIX, a highly expressed circRNA in NSCLC, exerted a repressive role in NSCLC malignant progression at least in part through targeting the miR-212-3p/ADAM10 axis, illuminating a novel understanding of circRNA regulation in NSCLC.

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Section: Discussionmentioning

confidence: 99%

<p>CircNFIX Acts as a miR-212-3p Sponge to Enhance the Malignant Progression of Non-Small Cell Lung Cancer by Up-Regulating ADAM10</p>

Lü¹,

Zhu²,

Qin³

et al. 2020

CMAR

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“…Osteosarcoma (OS) is a bone malignancy originating from osteoid bone tissue which has a high mortality rate (1,2). Despite the effectiveness of therapeutic modalities for OS, including surgical resection, neoadjuvant, or adjuvant radiotherapy or chemotherapy, the rates of mortality and metastasis among patients with the disease are still extremely high.…”

Section: Introductionmentioning

confidence: 99%

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI

Pan

Liu

et al. 2021

Ann Transl Med

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Background: Osteosarcoma (OS) is an aggressive bone cancer that most commonly affects adolescents and children. Emerging studies have shown that long noncoding RNA (lncRNA) performs essential roles in the occurrence and development of many tumors. Prostate androgen-regulated transcript 1 (PART 1) has been reported as a tumor oncogene; despite this, the mechanisms underlying its involvement in OS are unclear.Methods: OS and paired normal tissue samples were obtained, and gene expressions were detected by real time-quantitative polymerase chain reaction (RT-qPCR). The functions of PART 1 in OS cell proliferation, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8) and Transwell assays. Furthermore, the binding sites of PART 1 and miR-20b-5p as well as those between miR-20b-5p and bone morphogenic protein and activin membrane-bound inhibitor homolog (BAMBI) were verified by bioinformatics analysis and dual-luciferase reporter assay.Results: Our study found obvious overexpression of PART 1 in OS tissues and cells. Furthermore, PART 1 overexpression facilitated OS cell proliferation, invasion, and migration. Further mechanistic investigations revealed that PART 1 could sponge to miR-20b-5p, which was expressed at a low level in OS tissues and cells. Importantly, miR-20b-5p overexpression inhibited OS cell proliferation, invasion, and migration.Additionally, BAMBI was confirmed as a downstream gene of miR-20b-5p, and its expression was reversely modulated by miR-20b-5p and positively modulated by PART 1. Rescue experiments suggested that BAMBI was involved in PART 1-mediated promotion of OS progression.Conclusions: PART 1 serves as a competing endogenous RNA to promote OS tumorigenesis via its regulation of the miR-20b-5p/BAMBI axis, which may provide a promising therapeutic biomarkers for OS patients.

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“…We have previously reported that ZOL enhanced γ-ray radiation-induced DNA damage and suppressed OSA cell migration and invasion [34,35]. Recently, we also found that it significantly induced autophagy via modulation of microRNA (miRNA) expression [36]. In addition, increasing evidence showed that some miRNAs are involved in regulating tumor progression and relapse [37].…”

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confidence: 99%

Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells

Kim

Takahashi

et al. 2020

Cancers

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Osteosarcoma (OSA) is the most common malignant bone tumor in children and adolescents. The overall five-year survival rate for all bone cancers is below 70%; however, when the cancer has spread beyond the bone, it is about 15-30%. Herein, we evaluated the effects of carbon-ion beam irradiation alone or in combination with zoledronic acid (ZOL) on OSA cells. Carbon-ion beam irradiation in combination with ZOL significantly inhibited OSA cell proliferation by arresting cell cycle progression and initiating KHOS and U2OS cell apoptosis, compared to treatments with carbon-ion beam irradiation, X-ray irradiation, and ZOL alone. Moreover, we observed that this combination greatly inhibited OSA cell motility and invasion, accompanied by the suppression of the Pi3K/Akt and MAPK signaling pathways, which are related to cell proliferation and survival, compared to individual treatments with carbon-ion beam or X-ray irradiation, or ZOL. Furthermore, ZOL treatment upregulated microRNA (miR)-29b expression; the combination with a miR-29b mimic further decreased OSA cell viability via activation of the caspase 3 pathway. Thus, ZOL-mediated enhancement of carbon-ion beam radiosensitivity may occur via miR-29b upregulation; co-treatment with the miR-29b mimic further decreased OSA cell survival. These findings suggest that the carbon-ion beam irradiation in combination with ZOL has high potential to increase OSA cell death.Cancers 2020, 12, 698 2 of 15 increasing amount of evidence has demonstrated that high linear energy transfer (LET) carbon-ion radiation therapy is suitable for targeting many kinds of radioresistant tumors such as those associated with bone and soft tissue malignancies including OSA [9][10][11][12][13][14] because it primarily does not elicit cell cycle-and oxygen-dependent cell-killing effects; it also has a high potential to kill radiochemo-resistant cancer stem cells (CSCs) compared to low LET radiation [15][16][17][18][19]. However, although carbon ion beam radiotherapy treatment has yielded promising results, the prognosis of OSA still remains unsatisfactory; developing novel combinational therapeutic strategies to further improve overall survival is required.Bisphosphonates comprise the most important class of osteoclast-mediated bone resorption inhibitors and are used extensively for treating skeletal diseases such as postmenopausal osteoporosis and tumor-induced osteolysis [20,21]. Zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption that has demonstrated efficacy in treating bone metastases in cancer patients with breast, prostate, lung, and other solid tumors [22][23][24]. ZOL significantly enhances radiation-induced apoptosis and decreases cell viability, suggesting that it may exhibit radiosensitizing effects [25][26][27][28][29][30][31][32][33]. We have previously reported that ZOL enhanced γ-ray radiation-induced DNA damage and suppressed OSA cell migration and invasion [34,35]. Recently, we also found that it signi...

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Synergistic Autophagy Effect of miR-212-3p in Zoledronic Acid-Treated In Vitro and Orthotopic In Vivo Models and in Patient-Derived Osteosarcoma Cells

Cited by 12 publications

References 50 publications

<p>CircNFIX Acts as a miR-212-3p Sponge to Enhance the Malignant Progression of Non-Small Cell Lung Cancer by Up-Regulating ADAM10</p>

<p>CircNFIX Acts as a miR-212-3p Sponge to Enhance the Malignant Progression of Non-Small Cell Lung Cancer by Up-Regulating ADAM10</p>

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI

Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells

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