CEP55 as a promising biomarker and therapeutic target on gallbladder cancer

Huang, Maotuan; Zhong, Fuxiu; Chen, Mingyuan; Hong, Lingju; Chen, Weihong; Abudukeremu, Xiahenazi; She, Feifei; Chen, Yanling

doi:10.3389/fonc.2023.1156177

Cited by 5 publications

(3 citation statements)

References 63 publications

(68 reference statements)

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“… 22 High expression of CEP55 has also been associated with poor prognosis of non‐small cell lung cancer, gallbladder cancer, and endometrial cancer. 23 , 24 , 25 Chen et al identify 14 key genes related to the pathogenesis of colon cancer, including CEP55, TOP2A, RRM2, NCAPG2, providing new directions for elucidating the molecular mechanisms of colon cancer. 26 ASPM has also been shown to promote cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of TOP2A suppresses IL‐17 signaling pathway and alleviates the progression of ulcerative colitis

Li,

2024

Immunity Inflam & Disease

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BackgroundUlcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa, with a gradually increasing incidence. Therefore, it is necessary to actively seek targets for the treatment of UC.MethodsCommon differentially expressed genes (DEGs) were screened from two microarray data sets related to UC. Protein−protein interaction network was constructed to find the hub genes. The UC mouse model and cell model were induced by dextran sulfate sodium (DSS). The pathological changes of colon tissue were observed by hematoxylin‐eosin staining. Immunohistochemistry and immunofluorescence were performed to detect the expressions of Ki67 and Claudin‐1. The performance of mice was observed by disease activity index (DAI). The effect of TOP2A on proliferation, inflammation, oxidative stress, and interleukin‐17 (IL‐17) signaling pathway in UC model was measured by cell counting kit‐8, enzyme‐linked immunosorbent assay, and western blot.ResultsThrough bioinformatics analysis, 295 common DEGs were screened, and the hub gene TOP2A was selected. In UC model, there was obvious inflammatory cell infiltration in the colon and less goblet cells, while si‐TOP2A lessened it. More Ki67 positive cells and less Claudin‐1 positive cells were observed in UC model mice. Furthermore, knockdown of TOP2A increased the body weight and colon length of UC mice, while the DAI was decreased. Through in vivo and in vitro experiments, knockdown of TOP2A also inhibited inflammation and IL‐17 signaling pathway, and promoted proliferation in DSS‐induced NCM460 cells.ConclusionKnockdown of TOP2A alleviated the progression of UC by suppressing inflammation and inhibited IL‐17 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Knockdown of TOP2A suppresses IL‐17 signaling pathway and alleviates the progression of ulcerative colitis

Li,

2024

Immunity Inflam & Disease

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“…Immunohistochemistry analysis was performed as previously described [ 36 ]. Primary antibodies specific for TGF-β1 (1:500, Abcam), FOXA1 (1:400, Abcam), E-Cadherin (1:200, #3195), N-Cadherin (1:200, #13116), and Vimentin (1:300, #5741) were incubated overnight at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

TGF-β1 facilitates gallbladder carcinoma metastasis by regulating FOXA1 translation efficiency through m6A modification

Wu,

Ke,

Jiang

et al. 2024

Cell Death Dis

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TGF-β1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-β1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-β1 expression in GBC. Overexpression of FOXA1 inhibited TGF-β1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-β1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-β1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-β1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-β1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-β1 in regulating TGF-β1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.

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“…The CEP55 gene was overexpressed in GB carcinoma and associated with a decrease in apoptosis, advanced stage, lower cell differentiation, and dismal prognosis. Thus, it constitutes not only a diagnostic and prognostic biomarker but also a potent prospective therapeutic target[ 74 ].…”

Section: Diagnosismentioning

confidence: 99%

New trends in diagnosis and management of gallbladder carcinoma

Pavlidis,

Galanis,

Pavlidis

2024

World J Gastrointest Oncol

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Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.

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CEP55 as a promising biomarker and therapeutic target on gallbladder cancer

Cited by 5 publications

References 63 publications

Knockdown of TOP2A suppresses IL‐17 signaling pathway and alleviates the progression of ulcerative colitis

Knockdown of TOP2A suppresses IL‐17 signaling pathway and alleviates the progression of ulcerative colitis

TGF-β1 facilitates gallbladder carcinoma metastasis by regulating FOXA1 translation efficiency through m6A modification

New trends in diagnosis and management of gallbladder carcinoma

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