Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Gynecol Oncol. 2013 Sep;130(3):570-8. doi: 10.1016/j.ygyno.2013.06.004. Epub 2013 Jun 10.
Ras homolog gene family member C (RhoC) is a small G protein/guanosine triphosphatase involved in tumor mobility, invasion, and metastasis.
After RhoC siRNA transfection, we measured the changes in phenotypes and some relevant molecules in ovarian carcinoma cell, OVCAR3. The mRNA and protein expression of RhoC was detected in ovarian tumors.
RhoC siRNA transfection resulted in low growth, G1 arrest, and apoptotic induction in the OVCAR3 in comparison with the control and mock. Following RhoC knockdown, there was reduced mRNA or protein expression of protein kinase B (Akt), signal transducer and activator of transcription 3 (stat3), bcl-xL, surviving and phosphorylated p70S6 kinase (p-p70s6k), while the converse was true for Bax and caspase-3. Lovastatin induced apoptosis, suppressed proliferation, migration and invasion, and disrupted lamellipodia formation in OVCAR3. Lovastatin exposure induced lower RhoC, bcl-2, matrix metalloproteinase-9 (MMP-9), survivin, Akt, bcl-xL, vascular endothelial growth factor (VEGF), and p-p70s6k expression in OVCAR3 compared to the control, but higher caspase-3 and Bax expression. RhoC mRNA and protein expression was significantly higher in ovarian carcinoma than in benign tumors and normal ovary tissue (p<0.05) and was positively associated with dedifferentiation, FIGO staging and p-p70s6k expression of ovarian carcinoma (p<0.05).
The up-regulated RhoC expression may affect ovarian carcinogenesis and should be considered a good biomarker for the differentiation and progression of ovarian carcinoma. RhoC plays an important role in apoptosis by modulating the relevant genes and the phosphorylation of downstream p70s6k.
Ras 同源基因家族成员 C（RhoC）是一种参与肿瘤迁移、侵袭和转移的小 G 蛋白/鸟苷三磷酸酶。
在 RhoC siRNA 转染后，我们测量了卵巢癌细胞 OVCAR3 中表型和一些相关分子的变化。检测了卵巢肿瘤中 RhoC 的 mRNA 和蛋白表达。
与对照和模拟组相比，RhoC siRNA 转染导致 OVCAR3 生长缓慢、G1 期阻滞和凋亡诱导。RhoC 敲低后，蛋白激酶 B（Akt）、信号转导和转录激活因子 3（stat3）、bcl-xL、存活和磷酸化 p70S6 激酶（p-p70s6k）的 mRNA 或蛋白表达减少，而 Bax 和 caspase-3 则相反。洛伐他汀诱导 OVCAR3 凋亡，抑制增殖、迁移和侵袭，并破坏片状伪足形成。与对照组相比，洛伐他汀暴露导致 OVCAR3 中 RhoC、bcl-2、基质金属蛋白酶-9（MMP-9）、存活素、Akt、bcl-xL、血管内皮生长因子（VEGF）和 p-p70s6k 的表达降低，但 caspase-3 和 Bax 的表达升高。卵巢癌中 RhoC 的 mRNA 和蛋白表达明显高于良性肿瘤和正常卵巢组织（p<0.05），与卵巢癌的去分化、FIGO 分期和 p-p70s6k 表达呈正相关（p<0.05）。
上调的 RhoC 表达可能影响卵巢癌的发生，应被视为卵巢癌分化和进展的良好生物标志物。RhoC 通过调节相关基因和下游 p70s6k 的磷酸化在凋亡中发挥重要作用。
