Research Paper Volume 14, Issue 7 pp 3105—3128
Circular RNA_0006014 promotes breast cancer progression through sponging miR-885-3p to regulate NTRK2 and PIK3/AKT pathway
- 1 Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Received: December 28, 2021 Accepted: March 25, 2022 Published: April 5, 2022
https://doi.org/10.18632/aging.203996How to Cite
Copyright: © 2022 Zhou 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.
Abstract
Breast cancer is the most common cancer in women worldwide. Numerous reports have demonstrated that circRNAs play an essential role in regulating the biological characteristics of breast cancer. However, there are currently no reports regarding the role of hsa_circ_0006014 in breast cancer. In this study, qRT-PCR was used to detect the expression of hsa_circ_0006014 and related genes. MTT, colony formation and Transwell assays were used to explore the potential biological functions of hsa_circ_0006014 in breast cancer cells. Western blotting was used to explore the potential molecular mechanisms involving hsa_circ_0006014. In vivo experiments were used to evaluate the influence of hsa_circ_0006014 on animal tumors. In this study, we found higher expression of hsa_circ_0006014 in breast tumor samples than in matched adjacent normal samples, and its expression was positively correlated with histological grade (grade iii). Phenotypically, hsa_circ_0006014 promoted the proliferation of MDA-MB-231 and MCF-7 breast cancer cells. Mechanistically, there were confirmed binding sites between hsa_circ_0006014 and miR-885-3p, and hsa_circ_0006014 promoted breast cancer cell proliferation partially by sponging miR-885-3p and influenced CDK2/CCNE1 and CDK4/6/CCND1. Furthermore, we found that hsa_circ_0006014 regulated NTRK2 through miR-885-3p to modulate the PIK3/AKT signaling pathway. Our results demonstrated that hsa_circ_0006014 promotes breast cancer progression by sponging miR-885-3p to regulate the NTRK2/PIK3CA/AKT axis.
Abbreviations
DMEM: Dulbecco’s modified Eagle’s medium; NC: negative-control; MTT: (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; PCR: polymerase chain reaction; qRT-PCR: Quantitative reverse-transcription polymerase chain reaction; SDS: sodium dodecyl sulfate; CDK2: Cyclin Dependent Kinase 2; CCNE1: Cyclin E1; CDK4: Cyclin Dependent Kinase 4; CDK6: Cyclin Dependent Kinase 6; CCND1: Cyclin D1; NTRK2: Neurotrophic Receptor Tyrosine Kinase 2; MiRNAs: MicroRNAs; ILKAP: ILK Associated serine/threonine Phosphatase; PCNA: Proliferating Cell Nuclear Antigen; ceRNA: Competing Endogenous RNAs; PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; AKT: AKT serine/threonine kinase; RBPs: RNA binding proteins; ECM: Extracellular Matrix.