Abstract
Background: The purpose of the present investigation is to unravel the influence of the miR-375 inhibitor on cell survival descent and apoptosis stimulation, mediating PI3K/Akt/mTOR signaling network in human breast cancer cells. Methods: MCF-7 cells were transfected with miR-375 inhibitor for 72 h. Then, cell survival assay was measured by MTT. Cells were stained with EtBr/AO, DAPI, and DCFH-DA to assess the effect of the miR-375 inhibitor on cell death. A scratch experiment was performed to observe the cell migration ability. The expression of anti-apoptotic and apoptotic genes such as BCL-2, BAX, and PI3K/Akt/mTOR and miR-375 were evaluated in miR-375 inhibitor transfected cells by qRT-PCR. Findings: MiR-375 inhibitor sensitized tumor cells and influenced significant loss in the breast cancer cell proliferation with obvious cell death elevation. MiR-375 inhibitor effectively augmented ROS generation. Also, miR-375 inhibition hampered migratory ability. Furthermore, our qRT-PCR analysis showed that inhibition of the miR-375 was able to significantly reduce the constitutive expression of PI3K/Akt/mTOR mRNAs. Additionally, miR-375 suppression decreased the anti-apoptotic gene, Bcl- 2 expression and enhanced pro-apoptotic gene, Bax expression along with potentially decreasing miR-375 level compared to control. Novelty and applications: Inhibition of the miR-375 has considerably attenuated cell proliferation and stimulated apoptotic cell death in the breast cancer cells. Thus, miR-375 represent a potential therapeutic target for the breast cancer. Keywords: Breast Cancer; Proliferation; Apoptosis; Migration; miR-375
Highlights
Cancer is one of the leading causes of death worldwide, accounting for 1,92,92,789 (19.3 million) new cases and 99,58,133(9.9 million) deaths in 2020 alone
3.1 MiR-375 inhibition affects MCF-7 breast cancer cell proliferation MiR-375 inhibitor was transfected into MCF-7 cells and the cell proliferation rate was determined by MTT assay
The nuclei were dense in the miR-375 inhibitor transfected MCF-7 cells, and apoptotic bodies were observed in several dead cells
Summary
Cancer is one of the leading causes of death worldwide, accounting for 1,92,92,789 (19.3 million) new cases and 99,58,133(9.9 million) deaths in 2020 alone. The purpose of the present investigation is to unravel the influence of the miR-375 inhibitor on cell survival descent and apoptosis stimulation, mediating PI3K/Akt/mTOR signaling network in human breast cancer cells. The expression of anti-apoptotic and apoptotic genes such as BCL-2, BAX, and PI3K/Akt/mTOR and miR-375 were evaluated in miR-375 inhibitor transfected cells by qRT-PCR. Findings: MiR-375 inhibitor sensitized tumor cells and influenced significant loss in the breast cancer cell proliferation with obvious cell death elevation. Our qRT-PCR analysis showed that inhibition of the miR-375 was able to significantly reduce the constitutive expression of PI3K/Akt/mTOR mRNAs. miR-375 suppression decreased the anti-apoptotic gene, Bcl expression and enhanced pro-apoptotic gene, Bax expression along with potentially decreasing miR-375 level compared to control. Novelty and applications: Inhibition of the miR-375 has considerably attenuated cell proliferation and stimulated apoptotic cell death in the breast cancer cells. MiR-375 represent a potential therapeutic target for the breast cancer
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