Silencing of ASPP2 promotes the proliferation, migration and invasion of triple-negative breast cancer cells via the PI3K/AKT pathway

Abstract

Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and then enhancing the transcriptional activities toward pro‑apoptosis genes. ASPP2 has recently been reported to serve a major role in p53‑independent pathways. Triple‑negative breast cancer (TNBC) is a type of breast cancer that is more aggressive and highly lethal when p53 is mutated. In the present study, the mRNA level of ASPP2 was found to be suppressed in breast tumors compared with that in adjacent normal breast tissues, and the expression of ASPP2 was also decreased in a series of breast cancer cell lines compared with that in MCF‑10A normal breast cells. Downregulation of ASPP2 by specific small interfering RNA (siRNA) transfection was able to promote cell growth, reduce cell apoptosis, and contribute to cell migration and invasion. Furthermore, downregulation of ASPP2 promoted cell epithelial‑mesenchymal transition (EMT) in MDA‑MB‑231 and HCC‑1937 TNBC cells. Furthermore, it was found that when ASPP2 siRNA was transfected into MDA‑MB‑231 and HCC‑1937 cells, the expression of phosphoinositide‑3‑kinase regulatory subunit 1 (p85α) decreased and phosphorylation of protein kinase B (AKT) increased, which are key molecular regulators in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In conclusion, the present data indicated that ASPP2 had a crucial influence on the proliferation and metastasis in TNBC, and that the functional mechanism may be p53‑independent to a great extent. ASPP2 and its link with the PI3K/AKT pathway deserve further investigation and may provide novel insights into therapeutic targets for TNBC.

Mir‐30b‐5p Promotes Proliferation, Migration, and Invasion of Breast Cancer Cells via Targeting ASPP2

“…We observed that both mRNA and protein levels of ASPP2 were significantly reduced after miR-30b-5p overexpression (Figures 7(a) and 7(c)), and conversely, the mRNA and protein levels of ASPP2 were increased by transfection of miR-30b-5p inhibitor in both MDA-MB-231 and HCC 1937 cells (Figures 7(b) and 7(d)). Our prophase research found that as ASPP2 siRNA inhibited the expression of ASPP2, the expression of p-AKT increased [19]. In present study, we also found that miR-30b-5p transfection significantly promoted the expression of p-AKT, whereas miR-30b-5p inhibitor resulted in the reduction of p-AKT expression (Figures 7(c) to the ASPP2, inhibit its expression and lead to the p-AKT activation.…”

Upregulation of DAB2IP Inhibits Ras Activity and Tumorigenesis in Human Pancreatic Cancer Cells

“…The PI3K-AKT signaling pathway plays a central role in modulating cell proliferation, survival, and motility. 21,[24][25][26][27] In addition to promoting cell proliferation and survival, the PI3K-AKT pathway can also influence apoptotic cell death machinery. [24][25][26] DAB2IP promotes apoptosis by activating the ASK1, an upstream inducer of JNK and P38 MARK proteins.…”

Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line

“…It is important to note that the human male germ cell line TCam-2 originates from seminoma, which is a type of TGCT [19]. In this context, it is worth noting that almost all NANOS1-repressed pro-apoptotic factors identified in this study (GADD45A, GADD45B, GADD45G, RHOB, and TP53BP2) are well-established tumor suppressors [27][28][29][30][31][32][33][34][35]. This is in line with NANOS1 itself being proposed to promote carcinogenesis [36].…”