Knockdown of PLCB2 expression reduces melanoma cell viability and promotes melanoma cell apoptosis by altering Ras/Raf/MAPK signals

Abstract

Malignant melanoma has the highest malignancy rate among all skin cancer and is characterized by an insidious onset, high invasion and poor patient prognosis. Yet, the mechanisms involved remain unclear and warrant further investigation. Based on bioinformatic analysis, phospholipase c β2 (PLCB2) has been found to be correlated with melanoma growth. The present study was the first to demonstrate that PLCB2 is a key factor affecting melanoma proliferation and apoptosis. Here, microarray datasets from the publicly available Gene expression omnibus (Geo) database were employed, and gene set enrichment analysis (GSea) was introduced to identify candidate transcription factors. PLCB2 was identified as a crucial gene in the protein-protein interaction (PPi) network. The expression of PLCB2 mrna in various cancer lines was analyzed by reverse transcription-polymerase chain reaction (rT-Pcr). in addition, the proliferation ability and apoptosis rate in human melanoma cells overexpressing or not overexpressing PLCB2 were assessed using colony formation assay, flow cytometry and the Cell Counting Kit-8 (CCK-8) assay. Cell viability and apoptosis-related factors, such as p53, Bcl-2, Bax and caspase-3 were significantly regulated. Knockdown of PLCB2 suppressed the activation of the Ras/Raf/MAPK signaling pathway. In conclusion, knockdown of PLCB2 suppressed cell viability and promoted cell apoptosis by activating the Ras/Raf/MAPK pathway. Thus, PLCB2 may utilized as a potential therapeutic target in patients with melanoma.

Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

“…This pathway remains one of the promising therapeutic targets in cancer therapies due to its influential roles in cell proliferation, differentiation, apoptosis, growth and survival [97,98]. Lastly, the authors showed that PLCβ2 regulated the transition of cells from the G0/G1 phase to the G2/M phase, without altering the cell cycle proteins [77]. Thus, PLCβ2 may promote G2/M progression of melanoma cells, an essential event in cancer evolution.…”

“…Activated PLC isozymes are interconnected with several pathways, such as the PI3K/protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) pathway [76], RAS/rapidly accelerated fibrosarcoma (RAF)/mitogen activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) pathway [77], and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) [78] pathway that are major regulators of cell growth and proliferation in cancer cells (Figure 3). In the next paragraphs, we show how PLCs interact with these pathways to control cell growth, proliferation and survival in cancer.…”

“…In line with this microarray study is a recent functional study reporting that the knockdown of PLCβ2 expression in melanoma cells negatively affects cell viability and promotes cell apoptosis by altering p53 and pro-apoptotic proteins, caspase 3 and Bcl-2-associated X (Bax). Interestingly, PLCβ2 mediated these responses by activating the RAS/RAF/MAPK/ERK pathway [77]. This pathway remains one of the promising therapeutic targets in cancer therapies due to its influential roles in cell proliferation, differentiation, apoptosis, growth and survival [97,98].…”

The expression, prognostic value and potential mechanism of PLCB2 in clear cell renal cell carcinoma

“…They also demonstrated that PLCB2 highly expressed in breast cancer and associated with a poor prognosis. ZHANG et al revealed that PLCB2 could affect cell viability and apoptosis of melanoma by regulating the activation of Ras/Raf/MAPK signaling pathway [7]. Analogous correlations were found in leukemia, hepatocellular carcinoma, and Non-Small Cell Lung Carcinoma [8,9,10].…”

Differentially Expressed mRNAs and Their Long Noncoding RNA Regulatory Network with Helicobacter pylori-Associated Diseases including Atrophic Gastritis and Gastric Cancer

“…Studies have reported that RXFP4 was involved in the regulation of human neuroendocrine tumors [41,42]. Low expression of PLCB2 can change the 11 BioMed Research International RAS/Raf/MAPK signaling pathway, reduce cell viability, promote apoptosis, and inhibit tumorigenesis [43]. However, what role has these two molecules played in the process of NO-GA-GC remains poorly understood.…”