The long noncoding RNA AC093895.1 promotes ovarian cancer formation and metastasis through a positive feedback network dependent on the transcription factor SOX4

Recurrence and metastasis are the main causes of death in ovarian cancer (OC). Long non-coding RNAs (lncRNAs) are considered as good prognostic models and potential therapeutic targets for cancer patients because of their easy detection and strong correlation. Our study identifies an OC-associated lncRNA with tumor progression and therapeutic implications. It's found that lncRNA AC093895.1 is highly expressed in OC tissues and correlated with poor prognosis. AC093895.1 has a potentiating effect during the progression and metastasis of ovarian cancer. The effects of AC093895.1 on ovarian cancer cells are miR-1253 dependent. Results showed that by interacting with tumor-suppressive gene miR-1253 as competing endogenous RNA (ceRNAs), AC093895.1 significantly upregulated the downstream gene SOX4 of AC093895.1/ miR-1253 axis, leading to tumor metastasis. In addition, chromatin immunoprecipitation (ChIP) results further confirmed that SOX4 could bind to the AC093895.1 promoter, forming a positive feedback loop SOX4/AC093895.1/miR-1253/SOX4. Therapeutic strategy to break the loop through AC093895.1 knockdown exhibited attenuated OC growth and metastasis in vivo both in SK-OV-3 subcutaneous model and pulmonary metastatic model. Our study unveiled the potentiating effects of SOX4/AC093895.1/miR-1253/SOX4 on ovarian cancer cell survival, migration, and invasion. AC093895.1 may be a promising patient prognostic biomarker and therapeutic candidate. Created with BioRender.com.