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]
Summary
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
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