RASSF7 promotes cell proliferation through activating MEK1/2-ERK1/2 signaling pathway in hepatocellular carcinoma

Abstract

The Ras-association domain family (RASSF) proteins have been involved in many important biological processes. RASSF7 is recently reported to be up-regulated in several types of cancer. However, the function of RASSF7 remain unknown in human cancers. To explore the role of RASSF7 in hepatocellular carcinoma (HCC) cells proliferation and molecular mechanism. RASSF7 expression was examined using public database TCGA, qRT-PCR and Western blot. The correlation between RASSF7 and clinicopathological features was measured. Overexpression and silencing of RASSF7 were performed to measure the impact on HCC cell proliferation, cell cycle and apoptosis. Futhermore, the molecular mechanism of MEK1/2-ERK1/2 signaling pathway regulation by RASSF7 was explored. RASSF7 was significantly up-regulated in HCC tissues and cell lines, and correlated with AFP, poor tumor histology and T stage. Overexpression of RASSF7 promoted HCC cell proliferation, drived G1-S phase cell cycle transition and inhibited apoptosis. Knockdown of RASSF7 suppressed cell growth, induced G1-S phase cell cycle arrest and cell apoptosis. Furthermore, our findings also demonstrated that RASSF7 promoted HCC cell proliferation through activating MEK1/2-ERK1/2 signaling pathway. Taken together, this study provides a novel evidence for clinical significance of RASSF7 as a potential biomarker, and demonstrates that RASSF7-MEK1/2-ERK1/2 signaling pathway might be a novel pathway involved in HCC progression.

Expression Patterns of Ras-Association Domain Family Genes and Their Prognostic Values in Gastric Cancer

“…Previous studies have demonstrated that RASSF7 is up-regulated in hepatocellular carcinoma (HCC) 34 and non-small cell lung cancer 35 . Moreover, RASSF7 overexpression is signi cantly associated with increased serum alpha-fetoprotein levels, poor tumor histology, and T staging in HCC patients; overexpression of RASSF7 promotes the proliferation of HCC cells and cell cycle transformation in the G1-S phase, and inhibit cell apoptosis, whereas down-regulation of RASSF7 gene inhibits cell growth and induces cell cycle arrest and apoptosis in G1-S phase 34 . Although the present study indicates that RASSF7 might be used as a prognostic biomarker for gastric cancer, further clinical studies are needed to con rm its prognostic value.…”

Rassf7a promotes spinal cord regeneration and controls spindle orientation in neural progenitor cells

“…The detailed regulatory mechanisms are still unknown. Rassf7 has been shown earlier to regulate FGF/MEK/ERK signaling through binding to RAS proteins (Wang et al , 2016; Zhang et al , 2018a). Remarkably, the RAS‐regulated ERK signaling is also vital for the spindle orientation during lung tube development, suggesting a similar role of FGF during spindle polarity establishment (Tang et al , 2011).…”

“…RASSF7 has been suggested to play a role during mitosis through regulating microtubule dynamics (Sherwood et al , 2008; Recino et al , 2010; Gulsen et al , 2016). RASSF7 can promote cell proliferation through MEK1/2‐ERK1/2 signaling pathway activation (Wang et al , 2016; Zhang et al , 2018a). In vitro studies have also showed that, through interaction with N‐RAS, RASSF7 inhibits mitogen‐activated protein kinase kinase (MKK) 7 phosphorylation to negatively regulate pro‐apoptotic JNK signaling under stress‐induced conditions (Takahashi et al , 2011).…”

RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis

“…The N-terminal RASSF genes participate in numerous vital biological progresses, such as cell survival, apoptosis, tumor growth, and metastasis [ 7 ]. In addition, previous reports in the literature show RASSF7 expression is increased in NSCLC [ 10 ] and hepatocellular carcinoma [ 11 ] and plays a role in stimulating tumor proliferation. On the contrary, RASSF8 and RASSF10 have been shown to be reduced in multiple cancers, including lung cancer, gastric cancer, cervical cancer, breast cancer, colorectal esophageal squamous cell carcinoma, and hepatocarcinoma, and thus are considered as tumor suppressors [ 12 – 21 ].…”