Regulator of chromosome condensation 1 and broad-complex, tramtrack and bric a brac domain-containing protein is involved in ovarian cancer growth and drug resistance.

OBJECTIVE: Ovarian cancer (OC) is the most common and deadliest cancer in women worldwide. The high incidence and mortality rates highlight the serious threat that OC poses to women's health. Regulator of chromosome condensation (RCC1) and broad-complex, tramtrack and bric a brac ( BTB) domain-containing protein 1 (RCBTB1), which includes the RCC1 and BTB domains, is a cell proliferation-related protein. This study aims to reveal the role of RCBTB1 in OC and its possible pathway. MATERIAL AND METHODS: The expression of RCBTB1 in OC cells was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Transwell assay, wound-healing assay, clone formation assay, IHC, immunofluorescence, and methylthiazolyldiphenyl-tetrazolium bromide assay were used to evaluate the effect of silencing RCBTB1 in vivo and in vitro. The neurofibromin 1 (NF1)/rat sarcoma (Ras) signal axis was determined by Western Blot, qRT-PCR, and immunofluorescence. RESULTS: The A2780 cells had increased RCBTB1 expression (P < 0.01). By suppressing Ras signaling, RCBTB1 silencing hindered the proliferation of OC cells with Kirsten rat sarcoma viral oncogene (KRAS) mutations. RCBTB1 activated protein kinase kinase Cε, which degrades NF1. RCBTB1 also plays a key role in the Ras/ extracellular regulated protein kinase (ERK) signal axis by inhibiting Ras GTPase. RCBTB1 knockdown may alleviate mitogen-activated protein kinase kinase ( MEK) inhibitor resistance in KRAS-mutated OC by inhibiting Ras/ERK signaling. CONCLUSION: RCBTB1 may regulate the NF1/Ras signaling axis, which is critical for OC and MEK inhibitor resistance. This research offers a unique therapeutic approach for ovaries with KRAS mutations and uncovers a previously unknown connection between RCBTB1 and NF1/Ras signaling.