Cong Shen

LINC00654 promotes ovarian cancer progression by facilitating nuclear export of HuR and stabilizing oncogenic mRNAs

Ovarian cancer (OC) remains a significant challenge in oncology due to its late diagnosis and poor prognosis. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in cancer biology. Herein, we reported that LINC00654 was highly expressed in OC tissues and correlated with poor patient prognosis. In addition, LINC00654 silencing restrained OC cell proliferation and migration in vitro and in vivo. Mechanically, LINC00654 was identified to directly interact with Human antigen R (HuR), a known RNA-binding protein, through RNA pull-down, RNA immunoprecipitation (RIP), and cross‑linking immunoprecipitation (CLIP). Further analysis revealed that LINC00654 could induce the translocation of HuR from the nucleus to the cytosol, where it regulated the stability of its target oncogenes, such as VASH2. The stabilization of VASH2 subsequently activated the TGF-β pathway, which is known to play a critical role in cancer progression. Taken together, these findings establish a specific mechanism by which LINC00654 interacts with HuR, facilitates its nuclear export, and stabilizes VASH2, thereby activating the TGF-β pathway and promoting OC progression. This insight into LINC00654's role in OC provides potential therapeutic targets for intervention.

Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/β-catenin pathway

Abstract As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the β-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/β-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/β-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.