Liver X Receptor a Inhibits Osteosarcoma Cell Proliferation through Up-Regulation of FoxO1

Chang, Yue-wen; Zhao, Yongfang; Cao, Yuelong; Gu, Xiaosong; Liu, Zhiqiang; Wang, Shuqiang; Miao, Jinhao; Zhan, Hongsheng

doi:10.1159/000350134

Cited by 26 publications

(20 citation statements)

References 20 publications

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“…In lung cancer, FOXO1 negatively regulated activated EGFR signaling in both cell culture and in vivo models [25] and induction of FOXO1 by curcumin inhibited lung cancer progression and metastasis [26]. Moreover, in OS cells, FOXO1 expression status was negatively associated with proliferation [27]. Given the tumor suppressor role of FOXO1, in the present study, we found FOXO1 showed a converse expression pattern of miR-135b, and overexpression of FOXO1 significantly inhibited OS cells proliferation and invasion.…”

Section: Discussionsupporting

confidence: 56%

MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1

et al. 2014

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Recent data strongly suggest the important role of miRNAs in various cancer-related processes. Osteosarcoma (OS) is the most common primary cancer of the bone and usually leads to deaths due to its rapid proliferation and metastasis. Here, we demonstrated that compared with noncancerous bone tissues, miR-135b expression is frequently upregulated in OS specimens, inversely correlated with potential target-FOXO1 expression pattern. Bioinformatics analysis combined with experimental confirmation revealed FOXO1 is a direct target of miR-135b in OS. Functionally, miR-135b inhibitor significantly inhibited OS cells proliferation and invasion. Forced expression of FOXO1 showed the opposite effect, and FOXO1 knockdown abolished the effect of miR-135b inhibitor. Taken together, our data provide compelling evidence that miR-135b functions as an onco-miRNA in OS to promote OS cells proliferation and invasion, and its oncogenic effects are mediated chiefly through targeting FOXO1.

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Section: Discussionsupporting

confidence: 56%

MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1

et al. 2014

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“…*p<0.05 Here, we just focused on the direct targets downstream of miR-183 in controlling cell growth. Since FoxO1 plays a critical role in cell-cycle control [19,20] and has been shown to express in lung cells, we thus examined whether miR-183 may inhibit the expression of FoxO1. We either overexpressed or inhibited miR-183 expression in NSCLC cells, which decreased or increased the protein levels of FoxO1, respectively, without affecting FoxO1 transcript levels.…”

Section: Discussionmentioning

confidence: 99%

MiR-183 promotes growth of non-small cell lung cancer cells through FoxO1 inhibition

et al. 2015

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Non-small cell lung cancer (NSCLC) is a prevalent cancer in lung of high incidence. NSCLCs often appear to be fast growing, which renders comprehension of the mechanisms underlying the growth of NSCLC extremely critical. Previous study has addressed a role of microRNA (miR) family member, miR-183, in the regulation of the invasiveness of NSCLC, whereas the role of miR-183 in the growth control of NSCLC is not clear. Here, we analyzed the regulation of FoxO1 by miR-183 in vitro using luciferase-reporter assay. We also analyzed the effects of miR-183 on NSCLC cell growth in vitro using a microculture tetrazolium (MTT) assay and in vivo by visualizing tumor growth using bioluminescence assay. We found that overexpression of miR-183 in NSCLC cells decreased FoxO1 protein levels, whereas inhibition of miR-183 increased FoxO1 protein levels without affecting FoxO1 transcripts. Moreover, miR-183 bound to FoxO1 mRNA to prevent its translation through its 3'untranslated region (UTR). Furthermore, administration of miR-183 suppressed FoxO1 levels in NSCLC, resulting in a significant increase in NSCLC growth in vitro and in vivo, while administration of antisense of miR-183 significantly increased FoxO1 levels in NSCLC resulting in a significant decrease in NSCLC growth. Taken together, our data demonstrate that miR-183/FoxO1 axis may be a novel therapeutic target for regulating the growth of NSCLC.

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“…In the past years, the advances in chemotherapy has assisted general surgery to substantially improve the long-term survival of patients with nonmetastatic OS. However, the survival rate for patients with metastatic OS remains low [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

TIPE2 Mediates the Suppressive Effects of Shikonin on MMP13 in Osteosarcoma Cells

Deng¹,

Feng²,

Deng³

2015

Cell Physiol Biochem

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Background/Aims: Osteosarcoma (OS) is a primary malignant bone tumor in humans, and is notorious mainly for its distal metastases. We have recently shown that Shikonin, an effective constituent extracted from Chinese medicinal herb, inhibits OS cell invasion through suppression of matrix metalloproteinase 13 (MMP13). However, the underlying mechanisms remain unknown. Methods: Here, we studied the levels of tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in OS cells upon Shikonin treatment. TIPE2 levels were adapted in OS cell lines through transfection with plasmids carrying transgene or short-hairpin interference RNA (shRNA), and the effects of TIPE2 adaptation on MMP13 and cell invasiveness were evaluated by RT-qPCR, Western blot, ELISA and transwell cell migration assay, respectively. TIPE2 levels in OS specimens from patients were examined and correlated with cancer metastases and patient survival. Results: We found that Shikonin dose-dependently decreased MMP13 levels, and increased TIPE2 levels in two OS cell lines, U2OS and SaOS-2. Overexpression of TIPE2 in U2OS significantly suppressed MMP13 levels and cell invasiveness. Depletion of TIPE2 in SaOS-2 cells significantly increased MMP13 levels and cell invasiveness. Moreover, TIPE2 levels in OS specimens were significantly decreased, compared to adjacent non-cancer bone tissue. Lower TIPE2 levels correlated with higher incidence of metastases and worse 5-year survival. Conclusion: TIPE2 mediates the suppressive effects of Shikonin on MMP13 in osteosarcoma cells, and TIPE2 may be a novel therapeutic target for OS.

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Liver X Receptor a Inhibits Osteosarcoma Cell Proliferation through Up-Regulation of FoxO1

Cited by 26 publications

References 20 publications

MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1

MiR-135b promotes proliferation and invasion of osteosarcoma cells via targeting FOXO1

MiR-183 promotes growth of non-small cell lung cancer cells through FoxO1 inhibition

TIPE2 Mediates the Suppressive Effects of Shikonin on MMP13 in Osteosarcoma Cells

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