MCM7 silencing promotes cutaneous melanoma cell autophagy and apoptosis by inactivating the AKT1/mTOR signaling pathway

Abstract

Cutaneous melanoma (CM) has become a major public health concern. Studies illustrate that minichromosome maintenance protein 7 (MCM7) participate in various diseases including skin disease. Our study aimed to study the effects of MCM7 silencing on CM cell autophagy and apoptosis by modulating the AKT threonine kinase 1 (AKT1)/mechanistic target of rapamycin kinase (mTOR) signaling pathway. Initially, microarray analysis was used to screen the CM‐related gene expression data as well as differentially expressed genes. Subsequently, MCM7 expression vector and lentivirus RNA used for MCM7 silencing (LV‐shRNA‐MCM7) were constructed, and these vectors, dimethyl sulfoxide (DMSO) and AKT activator SC79 were then introduced into CM cell line SK‐MEL‐2 to validate the role of MCM7 in cell autophagy, viability, apoptosis, cell cycle, migration, and invasion. To further investigate the regulatory mechanisms of MCM7 in CM progress, the expression of MCM7, AKT1, mTOR, cyclin D1, as well as autophagy and apoptosis relative factors, such as LC3B, SOD2, DJ‐1, p62, Bcl‐2, Bax, and caspase‐3 in melanoma cells was determined. MCM7 might mediate the AKT1/mTOR signaling pathway to influence the progress of melanoma. MCM7 silencing contributed to the increased expression of Bax, capase‐3, and autophagy‐related genes (LC3B, SOD2, and DJ‐1), but decreased the expression of Bcl‐2, which suggested that MCM7 silencing promoted autophagy and cell apoptosis. At the same time, MCM7 silencing also attenuated cell viability, invasion, and migration, and reduced the cyclin D1 expression and protein levels of p‐AKT1 and p‐mTOR. Taken together, MCM7 silencing inhibited CM via inactivation of the AKT1/mTOR signaling pathway.

A DNA Replication-Independent Function of the pre-Replication Complex during Cell Invasion in C. elegans

“…Especially, increased expression of the regulatory subunit PIK3R2 has consistently been associated with an advanced tumor stage and enhanced metastasis formation [46]. Moreover, a link between MCM7 and the PI3K pathway has previously been reported for human melanoma [47] and esophagal squamous carcinoma [48], and an inhibitory role of the MCM7 locus on the PI3K antagonist PTEN was observed in a transgenic mouse model [49]. Likewise, depletion of mcm-7 in C. elegans also lead to reduced expression of the catalytic PI3K subunit age-1, while increasing PI3K pathway activity partially suppressed the AC invasion defect caused by mcm-7 depletion.…”

“…However, there exists a handful of reports associating pre-RC genes with cancer progression and increased cell migration [48,[58][59][60][61]. Notably, Lau et al observed reduced migration and invasion of human medulloblastoma cells after inhibition of MCM proteins [62].…”

MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

“…Knockdown of MCM7 can inhibit the proliferation of gastric cancer cells (46). Inhibition of MCM7 can promote autophagy and apoptosis of skin melanoma cells (47).…”

Integrative Analysis of Minichromosome Maintenance Proteins and Their Prognostic Significance in Melanoma

“…MCM7 was involved in oncogenic signaling pathways and was highly expressed in various tumor tissues, including melanoma. MCM7 silencing promoted autophagy and apoptosis, which inhibited the migration, viability, and invasion of tumor cells in melanoma ( 43 ). MCM7 was significantly correlated with tumorigenesis, progression, malignant conversion, and prognosis in skin squamous cell carcinoma ( 44 ).…”