Inhibited Expression of NLRP12 Promotes the Development of Triple-Negative Breast Cancer by Activating the NF-κB Pathway

NLRP12 can affect the progression of different diseases, including hepatocellular carcinoma. However, no report on triple-negative breast Cancer (TNBC) has been found. Thus, this study aimed to explore the role of NLRP12 in TNBC. In our study, immunohistochemistry, real-time quantitative PCR (qPCR), and Western blot assays were used to evaluate NLRP12 expression in TNBC tissues and cells. Then, NLRP12 lentivirus was constructed and infected into MDA-MB-231 and MDA-MB-157 cells with or without PTD-p65-P1 treatment. Next, cells were collected for cell function detection using the following procedures: colony formation assay for proliferation, Transwell for migration and invasion, and Western blot for NF-κB and MAPK pathway-associated proteins. Finally, a xenograft mouse model was applied; the tumor volume and weight were determined, and NLRP12, p-IκBb-α, and p-IκBb-α expressions were evaluated using qPCR and Western blot. Results indicated that NLRP12 was lowly expressed in TNBC tissues and cells. The inhibition of NLRP12 could induce the proliferation, migration, and invasion of TNBC cells, which also could be reversed by inhibiting the NF-κB pathway (PTD-p65-P1). Moreover, silencing of NLRP12 could upregulate p-IκBb-α, while IκBb-α, p-ERK, ERK, p-p38, p38, p-JNK, and JNK expressions remained unchanged, thereby indicating that only the NF-κB pathway could be activated by NLRP12 silencing. Furthermore, the xenograft mouse model confirmed the abovementioned findings. Therefore, the low expression of NLRP12 promoted the proliferation, migration, and invasion in TNBC cells by activating the NF-κB pathway. This study might provide insights into TNBC therapy.

Invasion; Migration; NF-κB; NLRP12; Proliferation; Triple-negative breast cancer.