Non-coding RNA RMRP governs RAB31-dependent MMP secretion, enhancing ovarian cancer invasion.

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Tác giả: Ji-Hye Ahn, Jung-Hye Choi, Jin-Hyung Kim, Tae Jin Kim, Jae-Hyung Lee, Ju-Seog Lee, Ki Jun Lee, Yong Sun Lee

Ngôn ngữ: eng

Ký hiệu phân loại: 149.73 Skepticism

Thông tin xuất bản: Netherlands : Biochimica et biophysica acta. Molecular basis of disease , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 703473

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.
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