Pan-Cancer analysis and experimental validation identify the oncogenic nature of ESPL1: Potential therapeutic target in colorectal cancer

Abstract

IntroductionExtra spindle pole bodies like 1 (ESPL1) are required to continue the cell cycle, and its primary role is to initiate the final segregation of sister chromatids. Although prior research has revealed a link between ESPL1 and the development of cancer, no systematic pan-cancer analysis has been conducted. Combining multi-omics data with bioinformatics, we have thoroughly described the function of ESPL1 in cancer. In addition, we examined the impact of ESPL1 on the proliferation of numerous cancer cell lines. In addition, the connection between ESPL1 and medication sensitivity was verified using organoids obtained from colorectal cancer patients. All these results confirm the oncogene nature of ESPL1.MethodsHerein, we downloaded raw data from numerous publicly available databases and then applied R software and online tools to explore the association of ESPL1 expression with prognosis, survival, tumor microenvironment, tumor heterogeneity, and mutational profiles. To validate the oncogene nature of ESPL1, we have performed a knockdown of the target gene in various cancer cell lines to verify the effect of ESPL1 on proliferation and migration. In addition, patients’ derived organoids were used to verify drug sensitivity.ResultsThe study found that ESPL1 expression was markedly upregulated in tumorous tissues compared to normal tissues, and high expression of ESPL1 was significantly associated with poor prognosis in a range of cancers. Furthermore, the study revealed that tumors with high ESPL1 expression tended to be more heterogeneous based on various tumor heterogeneity indicators. Enrichment analysis showed that ESPL1 is involved in mediating multiple cancer-related pathways. Notably, the study found that interference with ESPL1 expression significantly inhibited the proliferation of tumor cells. Additionally, the higher the expression of ESPL1 in organoids, the greater the sensitivity to PHA-793887, PAC-1, and AZD7762.DiscussionTaken together, our study provides evidence that ESPL1 may implicate tumorigenesis and disease progression across multiple cancer types, highlighting its potential utility as both a prognostic indicator and therapeutic target.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation

“…Increasing evidence indicates that ESPL1 participates in cell cycle signalling in breast cancer [ 32 ], endometrial cancer (UCEC) [ 33 ] and HCC [ 11 ], thus promoting the proliferation and migration of cancer cells [ 14 ]. However, in terms of BC, the potential pathways in which ESPL1 is involved still need to be better defined.…”

“…Extra spindle pole bodies like 1 (ESPL1) are cysteine endopeptidases, and these proteins participate in several aspects of the cell cycle by activating segregase [ 10 ]. There is growing evidence that high expression of ESPL1 is strongly associated with the development of malignant tumours, such as hepatocellular carcinoma (HCC) [ 11 ], glioma [ 12 ], lung adenocarcinoma (LUAD) [ 13 ] and colorectal cancer (CRC) [ 14 ]. In addition, Chen et al found that the high expression of ESPL1 was associated with the occurrence and recurrence of BC [ 15 ].…”

Identification of glycosyltransferase genes for diagnosing T-cell mediated rejection and predicting graft loss in kidney transplantation

“…Allogeneic kidney transplantation is the preferred treatment option for patients with end-stage renal disease, as it can signi cantly improve overall survival and quality of life [32]. However, graft rejection is a signi cant risk factor for long-term graft loss [5].…”