Knockdown of sal‐like 4 expression by small interfering RNA induces apoptosis in breast cancer cells

Abstract

Breast cancer is the most prevalent cancers worldwide and causes a significant amount of deaths annually. Spalt-like transcription factor 4 is known as a transcription factor, which has an important role in the proliferation of cancerous cells. Small interfering RNA (siRNA) is a short-chain molecule of 20 to 25 nucleotides that protrude on two sides of the 3′, two nucleotides. In this study, using a specific sequence of siRNA against the sequence of this gene, its activity is investigated in the cell line of breast cancer. The breast cancer cells (MCF-7) were cultured and then, using a specific anti-sal-like 4 (SALL4) siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and BCL-2 gene were measured using the real-time polymerase chain reaction method. The specific concentration of siRNA IC 50 of the SALL4 gene was 40.35 nmole. Gene expression results indicated that the expression of the Bcl-2 gene in the siRNA group was significantly reduced (P < 0.05). SiRNA can increase the apoptosis of breast cancer cells by reducing the gene expression of SALL4 gene and Bcl-2; it can be used as a novel targeted therapy. This strategy, in addition to increasing the specificity of the drug, also reduces the side effects when compared with conventional chemotherapy. K E Y W O R D S biomarker, breast cancer, diagnosis, spalt-like transcription factor 4 | INTRODUCTIONBreast cancer is accounted as the most common malignancy in women worldwide. Breast cancer can be affected by a wide range of internal and external factors and is also characterized by molecular heterogeneity 1,2 and drug resistance is the major obstacle for its successful chemotherapy. 3 Despite various existing screening programs and new therapeutic strategies including gene therapy, 4,5 cell therapy, 6-13 and using a new generation of drug delivery systems 14-21 finding and developing new diagnostic and therapeutic approaches in the treatment of various cancers such as breast cancer are required. [22][23][24][25][26][27] To enhance the therapeutic efficacy of breast cancer, it is imperative to understand profoundly the molecular pathogenesis of cancer cells as well as identify newer candidate genes/proteins, which are crucial in the proliferating and J Cell Biochem. 2019;120:9392-9399. wileyonlinelibrary.com/journal/jcb 9392 |

Effect of SALL4 on the Proliferation, Invasion and Apoptosis of Breast Cancer Cells

“…22 Previously, SALL4 has been shown to be essential for the regulation of cell proliferation and apoptosis in tumor cells. 23 The silencing of SALL4 resulted in cell cycle arrest and induced apoptosis in chronic myeloid leukemia cells. 24 Forced SALL4 expression in liver cancer cells increased cell proliferation and reduced the G1 phase cell population.…”

SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance

“…Overexpression of antiapoptotic Bcl-2 inhibits cell apoptosis and leads to an imbalance between enhanced proliferation and weakened programmed death through downregulation of Bax [73,74]. SALL4 overexpression in MDS and AML cells results in an increase in Bcl-2 expression and cell survival [75], whereas SALL4 knockdown markedly inhibits Bcl-2 expression in prostate cancer [76], breast cancer [16,77], colorectal cancer (CRC) [78], and nasopharyngeal carcinoma (NPC) [79], and it induces the expression of pro-apoptotic Bax in prostate cancer [76] and NPC [79].…”

The new advance of SALL4 in cancer: Function, regulation, and implication

“…The silenced SALL4 gene expression is associated with the inhibition of proliferation via cell cycle arrest at the G1/early S phase and apoptosis by decreasing the protein expression of Bcl‐2 in breast, colorectal, lung, and gastric cancer 15,44–49 . knockdown of SALL4 inhibits the proliferation of MCF‐7/ADR cells by arresting the cell cycle in the G1 phase, accompanied by a significant reduction of cyclin D1 and CDK4 expression 50 .…”