RNF12 Promotes Glioblastoma Malignant Proliferation via Destructing RB1 and Regulating MAPK Pathway

Abstract

Background. RNF12 has been linked to a variety of biological activities, including the control of the MDM2/P53 pathway, although its additional functions remain unclear. RNF12 was discovered to be a new ubiquitin ligase (E3) for RB1, amongst the most frequently repressed proteins in cancer of human. Method. Cell Counting Kit-8 was used to detect the cell proliferation; coimmunoprecipitation was used to determine that RNF12 interacts with RB1. Xenograft studies were used to verify the results. Result. In vivo and in vitro RNF12 interacts with RB1 regardless of E3 ligase activity. The ubiquitination of RB1 by RNF12 had an effect on its stability. RNF12 inhibits the RB1 protein and stimulates the MAPK pathway, promoting the growth of GBMs. Conclusion. Our findings show that RNF12 may operate as a tumour promoter by modulating the cancerous proliferation of glioblastoma by controlling the activity of a new RNF12/RB1/MAPK pathway regulatory axis and that this regulatory axis might be a valuable diagnostic focus in glioblastoma.

Ring finger protein 12 activates AKT signalling to promote the progression of liver cancer by interacting with EGFR

“…29 RNF12, as a member of the ring finger protein family, has been reported to be dysregulated in many malignancies. 12,13,30 RNF12 was reported to be overexpressed in glioblastoma, which was correlated with a poor prognosis. 13 Furthermore, RNF12 was found to interact with and target RB1 for degradation to stimulate the MAPK pathway and promote the malignant proliferation of glioblastoma.…”

“…Recently, increasing research showed that RNF12 was involved in the development of cancer 12 . In glioblastoma, RNF12 was reported to be highly expressed and related to poor prognosis of patients 13 . Meantime, RNF12 interacted with and ubiquitinated RB1 to induce its degradation, which activated the MAPK signalling pathway to promote the proliferation of glioblastoma 13 .…”

HOXC6 Regulates the Epithelial-Mesenchymal Transition through the TGF-β/Smad Signaling Pathway and Predicts a Poor Prognosis in Glioblastoma

“…No radiotherapy or chemotherapy was given before tissue collection. The OS was calculated based on the information collected from the date of diagnosis to the date of either death or last follow-up from 2019 to 2021 [ 23 ]. The NBTs were collected from patients with brain trauma.…”

“…After 24 h of culture, the cells that invaded the back of the membrane were stained using 0.1% crystal violet, followed by fixation with 4% PFA. Based on the total number of cells counted under the microscopy, the invasive capacity was calculated [ 23 ].…”

“…Tumors were paraffin-embedded after each trial [ 23 ]. The Institutional Animal Welfare Guidelines of the Chinese Academy of Medical Sciences authorized all animal care and research.…”