Abstract
Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR-876-5p level had a significant shorter overall survival compared to miR-876-5p high-expressing patients. In addition, gain-and loss-of-function experiments demonstrated that miR-876-5p restoration suppressed whereas miR-876-5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR-876-5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR-876-5p reduced c-Met abundance in OS cells and inversely correlated c-Met expression in OS tissues. Herein, c-Met was recognized as a direct target of miR-876-5p using lucif-erase reporter assay. Notably, c-Met restoration rescued miR-876-5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.
| Original language | English |
|---|---|
| Pages (from-to) | 3293-3301 |
| Number of pages | 9 |
| Journal | Journal of Cellular and Molecular Medicine |
| Volume | 23 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2019 |
Cite this
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MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma. / Xie, Weixin; Xiao, Jie; Wang, Tao; Zhang, Dongmei; Li, Zhanchun.
In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 5, 05.2019, p. 3293-3301.Research output: Contribution to journal › Article
TY - JOUR
T1 - MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma
AU - Xie, Weixin
AU - Xiao, Jie
AU - Wang, Tao
AU - Zhang, Dongmei
AU - Li, Zhanchun
PY - 2019/5
Y1 - 2019/5
N2 - Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR-876-5p level had a significant shorter overall survival compared to miR-876-5p high-expressing patients. In addition, gain-and loss-of-function experiments demonstrated that miR-876-5p restoration suppressed whereas miR-876-5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR-876-5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR-876-5p reduced c-Met abundance in OS cells and inversely correlated c-Met expression in OS tissues. Herein, c-Met was recognized as a direct target of miR-876-5p using lucif-erase reporter assay. Notably, c-Met restoration rescued miR-876-5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.
AB - Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR-876-5p level had a significant shorter overall survival compared to miR-876-5p high-expressing patients. In addition, gain-and loss-of-function experiments demonstrated that miR-876-5p restoration suppressed whereas miR-876-5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR-876-5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR-876-5p reduced c-Met abundance in OS cells and inversely correlated c-Met expression in OS tissues. Herein, c-Met was recognized as a direct target of miR-876-5p using lucif-erase reporter assay. Notably, c-Met restoration rescued miR-876-5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.
KW - c-Met
KW - metastasis
KW - miR-876-5p
KW - osteosarcoma
KW - proliferation
KW - EPITHELIAL-MESENCHYMAL TRANSITION
KW - PROMOTES TUMOR-GROWTH
KW - HEPATOCELLULAR-CARCINOMA
KW - CANINE OSTEOSARCOMA
KW - METASTASIS
KW - PROGRESSION
KW - EXPRESSION
KW - CANCER
U2 - 10.1111/jcmm.14217
DO - 10.1111/jcmm.14217
M3 - Article
VL - 23
SP - 3293
EP - 3301
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 5
ER -