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.

Highlights

  • Cervical cancer (CC) is the fourth major cause of mortality in women with an estimated 570,000 cases and 311,000 deaths worldwide in 2018 [1]

  • Results miR‐185‐3p Expression Decreases, While sex-determining region Y-box 2 (SOX2), cancer-associated transcript-1 (CCAT1) and Forkhead box protein 3 (FOXP3) Expressions Increase in CC Tissues, and SOX2 and CCAT1 Expressions are Linked to Tumor Size, Lymph Node Metastasis (LNM) and FIGO Stage When detecting the role of SOX2/CCAT1/miR-185-3p/ FOXP3 axis on the proliferation and self-renewal ability of CC stem cells, miR-185-3p, SOX2, CCAT1 and FOXP3 expressions in CC tissues and adjacent normal tissues were tested by RT-qPCR and western blot assay

  • It was manifested that (Fig. 1a–c) miR-185-3p expression was reduced, while SOX2, CCAT1 and FOXP3 expressions were increased in CC tissues

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Summary

Introduction

Cervical cancer (CC) is the fourth major cause of mortality in women with an estimated 570,000 cases and 311,000 deaths worldwide in 2018 [1]. This complex disease is participated in a variety of factors, including genetic effects and viral infection [2]. With the development of human papillomavirus co-testing and human papillomavirus vaccination, early diagnostic procedures of cervical dysplasia and cancer result in a reduction in the incidence, morbidity and mortality of CC [3]. It has revealed that SOX2 modulates radioresistance in CC by the hedgehog signaling pathway [7]. Another study has demonstrated that SOX2 is crucial for maintaining the subpopulation of cancer stem cells in CC cell lines [8].

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