Li Zhang1, Wei Zhang1, Zhigang Zuo1, Jiying Tang1, Ying Song1, Fengjun Cao1, Xiongjie Yu1, Shan Liu2, Xiaojun Cai3. 1. Department of Oncology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China. 2. Department of Oncology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China. uprdbq@163.com. 3. Department of Oncology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China. nauqaz@163.com.
Abstract
BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.
BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.
Authors: Fatima Domenica Elisa De Palma; Francesco Salvatore; Jonathan G Pol; Guido Kroemer; Maria Chiara Maiuri Journal: Biomedicines Date: 2022-03-21