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MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2.

Wang W, Zhou X, Wei M - Oncotarget (2015)

Bottom Line: Low-level expression of miR-144 was significantly associated with distant metastasis and poor prognosis.Furthermore, we identified Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) as direct targets for miR-144 binding, resulting in suppression of their expression.In clinical OS specimens, ROCK1 and ROCK2 levels were elevated, relative to that in paired normal bone tissues, and inversely correlated with miR-144 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

ABSTRACT
Osteosarcoma (OS) is the most common primary tumor of bone. MicroRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that are strongly implicated in cancerous processes. However, our current understanding of the biological role of miRNAs in OS remains incomplete. In the present study, miR-144 was markedly downregulated in OS cell lines and clinical specimens. Low-level expression of miR-144 was significantly associated with distant metastasis and poor prognosis. Functional studies demonstrated that ectopic expression of miR-144 suppresses tumor cell proliferation and metastasis in vitro as well as in vivo. Furthermore, we identified Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) as direct targets for miR-144 binding, resulting in suppression of their expression. Exogenous expression of ROCK1 or ROCK2 in 143B-miR-144 cells partially restored miR-144-inhibited cell proliferation and invasion. In clinical OS specimens, ROCK1 and ROCK2 levels were elevated, relative to that in paired normal bone tissues, and inversely correlated with miR-144 expression. Taken together, miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression, and may be a promising therapeutic target for OS.

No MeSH data available.


Related in: MedlinePlus

Downregulation of miR-144 in OS cell lines and tissues is associated with poor prognosisA. qRT-PCR was conducted to quantify endogenous expression of miR-144 in the human osteoblastic cell line, hFOB 1.19, and four OS cell lines, using U6 as the normalization control. B. miR-144 expression is frequently decreased in OS tissues. The left-hand panel shows expression of miR-144 in 24 paired OS and adjacent normal bone tissues. The right-hand panel shows miR-144 expression relative to adjacent normal tissues. Each bar represents the mean of 3 independent experiments. C. Kaplan-Meier analysis for overall survival in 67 OS patients in high- and low-risk groups based on miR-144 expression levels. *P < 0.05, **P < 0.01.
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Figure 1: Downregulation of miR-144 in OS cell lines and tissues is associated with poor prognosisA. qRT-PCR was conducted to quantify endogenous expression of miR-144 in the human osteoblastic cell line, hFOB 1.19, and four OS cell lines, using U6 as the normalization control. B. miR-144 expression is frequently decreased in OS tissues. The left-hand panel shows expression of miR-144 in 24 paired OS and adjacent normal bone tissues. The right-hand panel shows miR-144 expression relative to adjacent normal tissues. Each bar represents the mean of 3 independent experiments. C. Kaplan-Meier analysis for overall survival in 67 OS patients in high- and low-risk groups based on miR-144 expression levels. *P < 0.05, **P < 0.01.

Mentions: Initially, miR-144 expression was examined in four OS cell lines using quantitative real-time PCR (qRT-PCR). All OS cell lines tested displayed lower levels of miR-144 than the normal human osteoblastic cell line, hFOB 1.19 (Fig. 1A). Downregulation of miR-144 was also observed in clinical specimens, as evident from qRT-PCR analysis of 24 pairs of human primary OS tumors and adjacent normal bone tissues. In 66.7% (16 of 24) of the primary OS tissues, miR-144 expression was decreased by at least 2-fold (N/T ≥ 2-fold), compared to the adjacent non-tumor tissues (Fig. 1B).


MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2.

Wang W, Zhou X, Wei M - Oncotarget (2015)

Downregulation of miR-144 in OS cell lines and tissues is associated with poor prognosisA. qRT-PCR was conducted to quantify endogenous expression of miR-144 in the human osteoblastic cell line, hFOB 1.19, and four OS cell lines, using U6 as the normalization control. B. miR-144 expression is frequently decreased in OS tissues. The left-hand panel shows expression of miR-144 in 24 paired OS and adjacent normal bone tissues. The right-hand panel shows miR-144 expression relative to adjacent normal tissues. Each bar represents the mean of 3 independent experiments. C. Kaplan-Meier analysis for overall survival in 67 OS patients in high- and low-risk groups based on miR-144 expression levels. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496356&req=5

Figure 1: Downregulation of miR-144 in OS cell lines and tissues is associated with poor prognosisA. qRT-PCR was conducted to quantify endogenous expression of miR-144 in the human osteoblastic cell line, hFOB 1.19, and four OS cell lines, using U6 as the normalization control. B. miR-144 expression is frequently decreased in OS tissues. The left-hand panel shows expression of miR-144 in 24 paired OS and adjacent normal bone tissues. The right-hand panel shows miR-144 expression relative to adjacent normal tissues. Each bar represents the mean of 3 independent experiments. C. Kaplan-Meier analysis for overall survival in 67 OS patients in high- and low-risk groups based on miR-144 expression levels. *P < 0.05, **P < 0.01.
Mentions: Initially, miR-144 expression was examined in four OS cell lines using quantitative real-time PCR (qRT-PCR). All OS cell lines tested displayed lower levels of miR-144 than the normal human osteoblastic cell line, hFOB 1.19 (Fig. 1A). Downregulation of miR-144 was also observed in clinical specimens, as evident from qRT-PCR analysis of 24 pairs of human primary OS tumors and adjacent normal bone tissues. In 66.7% (16 of 24) of the primary OS tissues, miR-144 expression was decreased by at least 2-fold (N/T ≥ 2-fold), compared to the adjacent non-tumor tissues (Fig. 1B).

Bottom Line: Low-level expression of miR-144 was significantly associated with distant metastasis and poor prognosis.Furthermore, we identified Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) as direct targets for miR-144 binding, resulting in suppression of their expression.In clinical OS specimens, ROCK1 and ROCK2 levels were elevated, relative to that in paired normal bone tissues, and inversely correlated with miR-144 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

ABSTRACT
Osteosarcoma (OS) is the most common primary tumor of bone. MicroRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that are strongly implicated in cancerous processes. However, our current understanding of the biological role of miRNAs in OS remains incomplete. In the present study, miR-144 was markedly downregulated in OS cell lines and clinical specimens. Low-level expression of miR-144 was significantly associated with distant metastasis and poor prognosis. Functional studies demonstrated that ectopic expression of miR-144 suppresses tumor cell proliferation and metastasis in vitro as well as in vivo. Furthermore, we identified Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) as direct targets for miR-144 binding, resulting in suppression of their expression. Exogenous expression of ROCK1 or ROCK2 in 143B-miR-144 cells partially restored miR-144-inhibited cell proliferation and invasion. In clinical OS specimens, ROCK1 and ROCK2 levels were elevated, relative to that in paired normal bone tissues, and inversely correlated with miR-144 expression. Taken together, miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression, and may be a promising therapeutic target for OS.

No MeSH data available.


Related in: MedlinePlus