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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

ROCK1 and ROCK2 are upregulated in OS specimens and inversely correlated with miR-144 levelsA. ROCK1 and ROCK2 mRNA levels in 24 fresh OS specimens and adjacent normal bone tissues. B. Spearman's correlation analysis between miR-144 expression and ROCK1 or ROCK2 mRNA level. *P < 0.05, **P < 0.01.
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Figure 6: ROCK1 and ROCK2 are upregulated in OS specimens and inversely correlated with miR-144 levelsA. ROCK1 and ROCK2 mRNA levels in 24 fresh OS specimens and adjacent normal bone tissues. B. Spearman's correlation analysis between miR-144 expression and ROCK1 or ROCK2 mRNA level. *P < 0.05, **P < 0.01.

Mentions: Finally, ROCK1 and ROCK2 expression levels were measured in OS specimens and adjacent normal bone tissues. qRT-PCR analysis showed significantly higher mRNA levels of both ROCK1 and ROCK2 in OS, compared with normal bone tissue (Fig. 6A). Similarly, enrichment of ROCK1 and ROCK2 proteins were detected chiefly in tumor tissues, relative to normal bone tissues (Supplementary Fig. 4). Spearman's correlation analysis disclosed an inverse correlation between miR-144 expression and that of ROCK1 and ROCK2 (Fig. 6B).


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

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

ROCK1 and ROCK2 are upregulated in OS specimens and inversely correlated with miR-144 levelsA. ROCK1 and ROCK2 mRNA levels in 24 fresh OS specimens and adjacent normal bone tissues. B. Spearman's correlation analysis between miR-144 expression and ROCK1 or ROCK2 mRNA level. *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 6: ROCK1 and ROCK2 are upregulated in OS specimens and inversely correlated with miR-144 levelsA. ROCK1 and ROCK2 mRNA levels in 24 fresh OS specimens and adjacent normal bone tissues. B. Spearman's correlation analysis between miR-144 expression and ROCK1 or ROCK2 mRNA level. *P < 0.05, **P < 0.01.
Mentions: Finally, ROCK1 and ROCK2 expression levels were measured in OS specimens and adjacent normal bone tissues. qRT-PCR analysis showed significantly higher mRNA levels of both ROCK1 and ROCK2 in OS, compared with normal bone tissue (Fig. 6A). Similarly, enrichment of ROCK1 and ROCK2 proteins were detected chiefly in tumor tissues, relative to normal bone tissues (Supplementary Fig. 4). Spearman's correlation analysis disclosed an inverse correlation between miR-144 expression and that of ROCK1 and ROCK2 (Fig. 6B).

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