Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells

Veys, Clément; Jammes, Manon; Rédini, Françoise; Poulain, Laurent; Denoyelle, Christophe; Legendre, Florence; Galéra, Philippe

doi:10.3390/ph15030362

Cited by 9 publications

(23 citation statements)

References 40 publications

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“…The miRNAs in uence cancer cell initiation and metastasis [35] Our ndings show rst evidence that miR-342-5p is an important regulator in HCC resistance. miR-342-5p has been reported to be a potential tumor suppressor in neuroblastoma [36][37][38]. miR-342-5p mediated targeting of NAA10 suppresses colon cancer growth and induces apoptosis [39].…”

Section: Discussionmentioning

confidence: 99%

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR- 342-5p/CFL1

Nakka,

Jassi,

Chen

et al. 2023

Preprint

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Background Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. Methods MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. Results Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. Conclusion Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

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Section: Discussionmentioning

confidence: 99%

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR- 342-5p/CFL1

Nakka,

Jassi,

Chen

et al. 2023

Preprint

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“…EGFR phosphorylation is involved in the migration and invasion of OS mediated by Circular RNA cir-ITCH [ 36 ]. What’s more, it’s also researched that tumor-suppressive activity in OS is correlative with the downregulation of EGFR [ 37 , 38 ]. Through validation of target protein in the GEO dataset, we obtained SATB2 protein target exhibiting strong interaction with formononetin.…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer targets and molecular mechanisms of formononetin in treating osteosarcoma based on network pharmacology

Chen,

Zhou,

Weng

et al. 2023

Aging

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Osteosarcoma (OS) is a multifactorial bone malignancy that accounts for most cancers in children and adolescents. Formononetin has been proven to exhibit various pharmacological effects including anti-tumor, anti-obesity, anti-inflammation, and neuroprotective effects. Few studies have examined the pharmacological activities of formononetin in OS treatment, but the mechanism has not yet been completely elucidated. Network pharmacology is a new method based on the theory of system biology for analyzing the network of biological systems and selecting specific signal nodes for multi-target drug molecular design. Here, we used network pharmacology to explore the possible mechanism of formononetin in OS treatment. Human OS cell line MG63 was processed with four concentrations (0, 2, 5, 8 μg/mL) of formononetin. Subsequently, an MTT assay was performed to test cell proliferation and a scratch test was used to evaluate the migration ability of cancer cells. Caspase-3, p53, p21, and bcl-2 expression levels incubated with different concentrations of formononetin in MG63 cells were determined using Western blotting. After treated with formononetin for 48 h, MG63 cells exhibited marked apoptosis. The results revealed that certain concentrations of formononetin significantly exerted inhibitory effects on MG63 cell proliferation. Furthermore, formononetin decreased the bcl-2 level in MG63 cells but increased caspase-3, p21, and p53 levels in a concentration-dependent manner. Additionally, formononetin suppressed the expression of SATB2. Therefore, formononetin could dose-dependently inhibit MG63 cell proliferation and induce apparent cell apoptosis, providing a candidate treatment for OS, whereas SATB2 could be a potential prognostic biomarker for screening OS and therapeutic target of formononetin.

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“…Growing chondrosarcoma and osteosarcoma cells were seeded at 1x10 4 cells/cm 2 per 25 cm 2 flask. Cell lines were transfected 24 h after seeding with 20 nM of miRNA mimics using INTERFERin™ (Polyplus-Transfection) as described previously ( 26 , 27 ). An additional CDDP treatment was carried out after 48 h with each sublethal dose of CDDP as described previously ( 26 , 27 ).…”

Section: Methodsmentioning

confidence: 99%

“…One study has shown that pharmacological inhibition of Bcl-xL improves the sensitivity of osteosarcoma to doxorubicin ( 25 ). Furthermore, we previously showed that the direct inhibition of Bcl-xL by miR-491-5p and miR-342-5p induces apoptosis on osteosarcoma and chondrosarcoma cell lines ( 26 , 27 ). MiR-342-5p also directly inhibited the expression of Bcl-2 in some tested cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…We subsequently performed an individual and functional study with miR-16-1-3p, miR-646, miR-3667-3p and miR-4270. MiR-342-5p was used as a positive control because its tumor suppressive effects have already been validated on chondrosarcoma and osteosarcoma cells ( 26 , 27 ). For the SW1353 chondrosarcoma cell line, the potential cytotoxic and chemosensitizing effects of miRNAs were studied in normoxia and hypoxia, because hypoxia is representative of the in situ physiopathological micro-environment of the tumor ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

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MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells

Veys,

Boulouard,

Benmoussa

et al. 2023

Front. Oncol.

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Chondrosarcomas and osteosarcomas are malignant bone tumors with a poor prognosis when unresectable or metastasized. Moreover, radiotherapy and chemotherapy could be ineffective. MiRNAs represent an alternative therapeutic approach. Based on high-throughput functional screening, we identified four miRNAs with a potential antiproliferative effect on SW1353 chondrosarcoma cells. Individual functional validations were then performed in SW1353 cells, as well as in three osteosarcoma cell lines. The antiproliferative and cytotoxic effects of miRNAs were evaluated in comparison with a positive control, miR-342-5p. The cytotoxic effect of four selected miRNAs was not confirmed on SW1353 cells, but we unambiguously revealed that miR-4270 had a potent cytotoxic effect on HOS and MG-63 osteosarcoma cell lines, but not on SaOS-2 cell line. Furthermore, like miR-342-5p, miR-4270 induced apoptosis in these two cell lines. In addition, we provided the first report of Bcl-xL as a direct target of miR-4270. MiR-4270 also decreased the expression of the anti-apoptotic protein Mcl-1, and increased the expression of the pro-apoptotic protein Bak. Our findings demonstrated that miR-4270 has tumor suppressive activity in osteosarcoma cells, particularly through Bcl-xL downregulation.

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Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells

Cited by 9 publications

References 40 publications

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR- 342-5p/CFL1

Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR- 342-5p/CFL1

Anti-cancer targets and molecular mechanisms of formononetin in treating osteosarcoma based on network pharmacology

MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells

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