Knockdown of STMN1 enhances osteosarcoma cell chemosensitivity through inhibition of autophagy

Wang, Zili; He, Rongzhen; Xia, Hansong; Yu, Wei; Wu, Song

doi:10.3892/ol.2017.5941

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…Jiang et al (41) reported that the inhibition of STMN1 expression using small interfering RNA induced growth inhibition, cell cycle arrest and apoptosis. Other researchers have reported that STMN1 may be involved in the drug resistance of osteosarcoma, and inhibition of STMN1 enhanced the chemosensitivity of osteosarcoma cells (42)(43)(44). In the present study, pMSCV-STMN1 reversed miR-193b-induced inhibition of migration and invasion in F5M2 cells, indicating that miR-193b may inhibit migration and invasion of osteosarcoma through STMN1.…”

Section: Discussionsupporting

confidence: 68%

miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma

Gao

Yang

et al. 2020

Oncol Rep

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Emerging evidence has indicated that microRNAs (miRs) are involved in the malignant behavior of cancer. The present study explored the role of miR-193b in the development and metastasis of osteosarcoma. Compared with F4 osteosarcoma cells, which have a relatively low metastatic potential, highly metastatic F5M2 cells exhibited a lower expression of miR-193b. Furthermore, miR-193b exerted negative effects on cell proliferation, colony formation, cell cycle progression, migration and invasion, and induced apoptosis. In vivo studies revealed negative influences of miR-193b on tumorigenesis and metastasis. The tumor-suppressive role of miR-193b was achieved by targeting KRAS and stathmin 1 (STMN1). Notably, overexpression of KRAS and STMN1 attenuated the miR-193b-induced inhibition of malignant behaviors. There was a double-negative regulatory loop between MYC and miR-193b, with MYC inhibiting miR-193b expression by directly binding to its promoter region and miR-193b negatively influencing MYC expression indirectly through some unknown mechanism. Collectively, these findings indicated that miR-193b may serve a tumor suppressive role in osteosarcoma by targeting KRAS and STMN1. The double-negative regulatory loop between MYC and miR-193b may contribute to the sustained upregulation of MYC, the downregulation of miR-193b, and to the subsequently enhanced expression of KRAS and STMN1, which may eventually lead to the development and metastasis of osteosarcoma.

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Section: Discussionsupporting

confidence: 68%

miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma

Gao

Yang

et al. 2020

Oncol Rep

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“…The oncogenic role of STMN1 has been previously demonstrated in several types of cancer or in cancer cell lines [ 25 ]. In osteosarcoma cells, knockdown of the STMN1 gene was previously shown to enhance chemosensitivity of osteosarcoma cells to paclitaxel through inhibition of autophagy [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although studies on the role of STMN1 in human osteosarcoma are lacking, a recently published in vitro study of human osteosarcoma cell lines showed that knockdown of the STMN1 gene enhanced osteosarcoma cell chemosensitivity by inhibiting autophagy, indicating that STMN1 might be a potential target for the treatment of chemoresistance in osteosarcoma [ 13 ]. However, the clinical significance of STMN1 expression in human osteosarcoma in vivo remains to be elucidated, and the underlying molecular mechanisms for the effects of STMN1 are still unknown.…”

Section: Introductionmentioning

confidence: 99%

An Immunohistochemical Study of Stathmin 1 Expression in Osteosarcoma Shows an Association with Metastases and Poor Patient Prognosis

Zhao

Wang

et al. 2018

Med Sci Monit

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BackgroundOsteosarcoma is the most common primary bone cancer and has a broad spectrum of histological subtypes. Stathmin 1 (STMN1) is a cytosolic phosphoprotein that is expressed in several types of cancer. The aim of this study was to evaluate the expression levels of STMN1 in osteosarcoma with clinicopathological characteristics and patient prognosis.Material/MethodsThe expression of STMN1 in tumor tissue from 94 patients with OS was detected and evaluated using an immunohistochemical score to divide the patients into low expression and high expression groups. Correlation between STMN1 expression and clinicopathological factors were analyzed with Fisher’s test, the prognostic value of expression levels of STMN1 in tumor tissue was evaluated by Kaplan-Meier univariate analysis, and independent prognostic factors were identified using the Cox regression model.ResultsLow expression of STMN1 was found in 43.62% of cases and high expression of STMN1 was found in 56.38% of cases of osteosarcoma. High tumor expression of STMN1 was significantly associated with the presence of metastases (P=0.028), Enneking surgical stage (P=0.030), tumor response to chemotherapy (P=0.011), and the site of tumor origin (P=0.023). High tumor expression of STMN1 was a prognostic marker in patients with osteosarcoma for poor prognosis (P=0.016), poor response to chemotherapy (P=0.004), the presence of metastases (P=0.003), advanced Enneking surgical stage (P=0.014), and the chondroblastic osteosarcoma subtype (P=0.004). The expression STMN1 was identified as an independent prognostic biomarker of osteosarcoma.ConclusionsIncreased expression of STMN1 in tumor tissue was an independent prognostic biomarker in patients with osteosarcoma.

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“…Melanoma cells invade skin tissue and enter blood vessels, forming metastases at distant sites [ 2 ]. In addition, we have found that STMN1, a cytosolic phosphoprotein [ 3 ], and SSBP1, involved in p53 transcriptional activity [ 4 ], are up- and down-regulated, respectively, in melanoma cells and that their modulation is involved in melanoma transformation [ 5 ]. It has also been reported that the mutation rate in melanoma is higher than in other solid malignancies.…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

Deiana

Carbonare

Serena

et al. 2018

Cells

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The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy.

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Knockdown of STMN1 enhances osteosarcoma cell chemosensitivity through inhibition of autophagy

Cited by 11 publications

References 29 publications

miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma

miR‑193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma

An Immunohistochemical Study of Stathmin 1 Expression in Osteosarcoma Shows an Association with Metastases and Poor Patient Prognosis

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

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