Lee Ki Jun, Ahn Ji-Hye, Kim Jin-Hyung, Lee Yong Sun, Lee Ju-Seog, Lee Jae-Hyung, Kim Tae Jin, Choi Jung-Hye
Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, South Korea; College of Pharmacy, Kyung Hee University, South Korea.
Department of Korean Pharmacy, College of Pharmacy, Woosuk University, South Korea.
Biochim Biophys Acta Mol Basis Dis. 2025 Jun;1871(5):167781. doi: 10.1016/j.bbadis.2025.167781. Epub 2025 Mar 6.
Non-coding RNAs (ncRNAs) are frequently dysregulated in various cancers and have been implicated in the etiology and progression of cancer. Ovarian cancer, the most fatal gynecological cancer, has a poor prognosis and a high patient fatality rate due to metastases. In this study, we classified patients with ovarian cancer into three groups based on their ncRNA expression levels. Notably, an ncRNA transcribed by RNA polymerase III, RNA component of mitochondrial RNA processing endoribonuclease (RMRP), is highly expressed in a group with a poor prognosis. Functional assays using SKOV3 and HeyA8 human ovarian cancer cell lines revealed that while RMRP modulation had no significant effect on cell viability, it markedly enhanced cell invasion. Knockdown and ectopic expression experiments demonstrated that RMRP promotes the secretion of matrix metalloproteinase (MMP)-2 and -9, thereby facilitating ovarian cancer cell invasiveness. Transcriptomic analysis further revealed a positive correlation between RMRP expression and genes involved in cellular localization, including RAB31, a member of the Ras-related protein family. Notably, RAB31 knockdown abrogated the pro-invasive effects of RMRP, identifying it as a key downstream effector in SKOV3 and HeyA8 cells. In addition, MechRNA analysis identified RAB31 as a putative RMRP-interacting transcript. These findings establish RMRP as a critical regulator of RAB31-dependent MMP secretion and ovarian cancer cell invasion. Moreover, our results suggest that RMRP could serve as a promising prognostic biomarker for ovarian cancer.
非编码RNA（ncRNAs）在多种癌症中经常发生失调，并与癌症的病因和进展有关。卵巢癌是最致命的妇科癌症，由于转移，其预后较差，患者死亡率较高。在本研究中，我们根据ncRNA表达水平将卵巢癌患者分为三组。值得注意的是，一种由RNA聚合酶III转录的ncRNA，线粒体RNA加工内切核糖核酸酶的RNA成分（RMRP），在预后较差的一组中高度表达。使用SKOV3和HeyA8人卵巢癌细胞系进行的功能分析表明，虽然RMRP调节对细胞活力没有显著影响，但它显著增强了细胞侵袭。敲低和异位表达实验表明，RMRP促进基质金属蛋白酶（MMP）-2和-9的分泌，从而促进卵巢癌细胞的侵袭性。转录组分析进一步揭示了RMRP表达与参与细胞定位的基因之间的正相关，包括Ras相关蛋白家族的成员RAB31。值得注意的是，RAB31敲低消除了RMRP的促侵袭作用，确定其为SKOV3和HeyA8细胞中的关键下游效应物。此外，MechRNA分析确定RAB31为推定的RMRP相互作用转录本。这些发现确立了RMRP作为RAB31依赖性MMP分泌和卵巢癌细胞侵袭的关键调节因子。此外，我们的结果表明，RMRP可以作为卵巢癌一个有前景的预后生物标志物。
