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Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis
Caijun Dong1, Liangwei Yang2, Guofang Zhao1
1Department of Thoracic Surgery, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
Abstract:
Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.
Insights
Circular phosphoglycerate mutase 1 (circ-PGAM1) enhances matrine resistance in non-small cell lung cancer (NSCLC) by regulating the miR-326/CXCR5 pathway. This finding offers new therapeutic strategies for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Circular RNAs (circRNAs) play roles in tumor progression, including drug resistance.
- The specific role of circ-PGAM1 in matrine resistance in non-small cell lung cancer (NSCLC) is not well understood.
Purpose of the Study:
- To investigate the role of circ-PGAM1 in matrine resistance in NSCLC.
- To elucidate the underlying molecular mechanism involving the miR-326/CXCR5 axis.
Main Methods:
- Gene expression analysis using RT-qPCR.
- Assessment of cell proliferation and apoptosis via colony formation and TUNEL assays.
- Investigation of molecular interactions using miRNA inhibition and target gene identification.
Main Results:
- circ-PGAM1 was upregulated in NSCLC cells compared to normal lung cells.
- Overexpression of circ-PGAM1 conferred resistance to matrine by promoting proliferation and inhibiting apoptosis.
- circ-PGAM1 interacts with miR-326, and its knockdown enhances matrine's antitumor effects, which can be reversed by inhibiting miR-326.
- CXCR5 was identified as a downstream target of miR-326.
Conclusions:
- circ-PGAM1 promotes matrine resistance in NSCLC cells through the miR-326/CXCR5 pathway.
- Targeting the circ-PGAM1/miR-326/CXCR5 axis may represent a novel therapeutic strategy for NSCLC.

