SOX2 Regulates lncRNA CCAT1/MicroRNA-185-3p/FOXP3 Axis to Affect the Proliferation and Self-Renewal of Cervical Cancer Stem Cells

Nanoscale Res Lett. 2021 Jan 4;16(1):2. doi: 10.1186/s11671-020-03449-z.

Abstract

It has been presented the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We aim to discuss the effect of sex-determining region Y-box 2 (SOX2)/lncRNA colon cancer-associated transcript-1 (CCAT1)/microRNA-185-3p (miR-185-3p)/forkhead box protein 3 (FOXP3) on the proliferation and self-renewal ability of CC stem cells. MiR-185-3p, SOX2, CCAT1 and FOXP3 expressions were tested in CC tissues and cells. The relationship between SOX2/CCAT1 expression and clinicopathological features in CC patients was verified. Loss- and gain-of-function investigations were conducted in CD44+HeLa cells to discuss biological functions and self-renewal capacity. Finally, the relationships among SOX2, CCAT1, FOXP3 and miR-185-3p were verified. miR-185-3p expression was decreased, while SOX2, CCAT1 and FOXP3 expressions were increased in CC tissues and cells. SOX2 and CCAT1 expressions were linked to tumor size, lymph node metastasis and international federation of gynecology and obstetrics stage of CC. Down-regulating SOX2 or CCAT1 and up-regulating miR-185-3p resulted in inhibition of proliferation, invasion, migration and cell sphere number as well as apoptosis acceleration of CD44+HeLa cells. SOX2 could bind to CCAT1 which affected miR-185-3p expression, and FOXP3 was targeted by miR-185-3p.

Keywords: Cervical cancer; Colon cancer-associated transcript-1; Forkhead box protein 3; MicroRNA-185-3p; Proliferation; Self-renewal; Sex-determining region Y-box 2.