Abstract

Objective Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients. Materials and Methods Herein, two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The levels of IL-10 mRNA, miR-944, and circ_ZFR were measured using qRT-PCR analyses. The CCK-8 assay was used to determine PTX resistance. The IL-10 expression was measured via the ELISA technique. The combination of miR-944 and circ_ZFR or IL-10 was validated using a dual-luciferase reporter (DLR) assay. Results The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells. Conclusion circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression.

Highlights

  • According to the global survey of cancer statistics, cervical cancer (CC) is considered to be the fourth most prevalent malignancy in women despite the HPV vaccination and testing [1, 2]

  • CC has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy

  • CircRNAs are a type of unique noncoding RNA [4, 5] without 3′ and 5′ ends. Both ends are covalently connected which provides a circular shape to the RNA molecule [6, 7]. circRNAs were originally considered as splicing defects [8]; numerous studies have shown that these RNAs with abnormal expression have a key role in the advancement of various malignancies [9,10,11,12], including CC [13, 14]. circRNAs have been shown to influence chemoresistance [15,16,17]. circ_ZFR promotes CC progression by Rb phosphorylation and through regulating the SSBP1/ CDK2/cyclin E1 complex [18]

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Summary

Objective

Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients. Two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The CCK-8 assay was used to determine PTX resistance. The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. Circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells. Circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression Conclusion. circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression

Introduction
Materials and Methods
Results
Discussion
Conflicts of Interest

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