Research Paper Volume 13, Issue 4 pp 5986—6009
Overexpression of hsa_circ_0002874 promotes resistance of non-small cell lung cancer to paclitaxel by modulating miR-1273f/MDM2/p53 pathway
- 1 Department of Pathology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan 215300, Jiangsu, PR China
- 2 Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, Zhejiang, PR China
- 3 Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China
- 4 Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China
- 5 Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China
Received: July 17, 2020 Accepted: December 19, 2020 Published: February 17, 2021https://doi.org/10.18632/aging.202521
How to Cite
Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance.
Methods: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis.
Results: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2.
Conclusions: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/MDM2/P53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.