Circ_MACF1 Targets MiR-421 to Upregulate FMO2 to Suppress Paclitaxel Resistance and Malignant Cellular Behaviors in Lung Adenocarcinoma

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2023 Oct 10

PMID 37814902

Authors

Xiaoting Qian

Chunhua Chen

Sanxiang Tong

Jun Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Chemoresistance remains an enormous challenge in the treatment of lung adenocarcinoma (LADC). Circular RNAs (circRNAs) exhibit important regulation in tumor progression and chemoresistance. This research focused on exploring the regulatory function and mechanism of circ_MACF1 (has_circ_0011780) in paclitaxel (PTX) resistance in LADC.

Methods: Circ_MACF1, miR-421 and flavin-containing monooxygenase 2 (FMO2) were determined by RT-qPCR. MTT was applied to detect IC of PTX. The proliferation analysis was performed using EdU and colony formation assay. Cell apoptosis and motility were examined using flow cytometry and transwell assay, respectively. Western blot was administered for protein detection. A dual-luciferase reporter assay was performed for confirming target interaction. PTX sensitivity in vivo was researched via xenograft tumor assay.

Results: Expression of circ_MACF1 was decreased in PTX-resistant LADC tissues and cells. Circ_MACF1 overexpression reduced chemoresistance, proliferation, motility and accelerated apoptosis in PTX-resistant LADC cells. Circ_MACF1 targeted miR-421 and miR-421 upregulation reverted circ_MACF1-evoked effects. FMO2 served as a downstream target of miR-421 and circ_MACF1 sponged miR-421 to elevate the expression of FMO2. MiR-421 enhanced PTX resistance and LADC progression via targeting FMO2. FMO2 knockdown enhanced IC of PTX and cell proliferation. In vivo, circ_MACF1 elevated PTX sensitivity of LADC by mediating miR-421/FMO2 axis.

Conclusion: These findings elucidated that circ_MACF1 inhibited PTX resistance by absorbing miR-421 to upregulate FMO2 in LADC.

Citing Articles

Circ_MACF1 targets miR-421 to upregulate FMO2 to suppress paclitaxel resistance and malignant cellular behaviors in lung adenocarcinoma.

Qian X, Chen C, Tong S, Zhang J Thorac Cancer. 2023; 14(33):3348-3357.

PMID: 37814902 PMC: 10665787. DOI: 10.1111/1759-7714.15132.

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