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Expression Level of Small Nuclear Ribonucleoprotein D1 in Gastric Cancer and Its Effect on Prognosis
YINLixia, YANGJingjing, NIUMinzhu, GENGZhijun, LIJiangyan, LIJing
Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (1) : 1-9.
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Abbreviation (ISO4): Acta Academiae Medicinae Sinicae
Editor in chief: Xuetao CAO
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Expression Level of Small Nuclear Ribonucleoprotein D1 in Gastric Cancer and Its Effect on Prognosis
Objective To investigate the expression of small nuclear ribonucleoprotein D1 (SNRPD1) in the gastric cancer tissue and evaluate the predictive value of SNRPD1 expression level for the long-term prognosis of gastric cancer patients and the possible functioning mechanism of SNRPD1. Methods The UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) were employed to analyze the expression level of SNRPD1 in pan-cancer and its relationship with the prognosis of gastric cancer.The clinical data of 109 patients who underwent radical surgery for gastric cancer from January 2014 to January 2017 in the First Affiliated Hospital of Bengbu Medical University were retrospectively analyzed.Gastric cancer and paracancerous tissue samples were collected,and the expression of SNRPD1 was detected by immunohistochemical staining.Lentiviral transfection was employed to construct the BGC-823 gastric cancer cell models with stable high and low expression of SNRPD1,respectively.The CCK-8 assay and colony formation assay were employed to measure the proliferation of gastric cancer cells,and flow cytometry was used to analyze the cell cycle.Western blotting was employed to determine the expression levels of proteins in the signaling pathway. Results The data from UALCAN and GEPIA showed that SNRPD1 was highly expressed in the tissue of malignant tumors including gastric cancer (P<0.001).The expression level of SNRPD1 in the gastric cancer tissue was higher than that in the paracancerous tissue (P<0.001).Moreover,the expression level of SNRPD1 was positively correlated with the levels of carcinoembryonic antigen (P<0.001),carbohydrate antigen 19-9 (P<0.001),G stage (P=0.042),T stage (P=0.002),and N stage (P=0.027) in the patients with gastric cancer.The high expression of SNRPD1 had a predictive value for the long-term prognosis of gastric cancer (P<0.001),and it was an independent risk factor for the death of gastric cancer patients (P=0.003).The results of gene ontology and kyoto encyclopedia of genes and Genomes enrichment analyses showed that SNRPD1 was involved in the regulation of the cell cycle.The results of CCK-8 and colony formation assays showed that up-regulation of SNRPD1 promoted the proliferation of gastric cancer cells (P<0.001,P<0.001).The up-regulation of SNRPD1 up-regulated the expression of cyclin-dependent kinase 6 and G1/S-specific cyclin-D1 (P<0.001,P=0.002),whereas the interference in SNRPD1 led to opposite results (P=0.004,P<0.001).SNRPD1 accelerated the G1/S phase transition of gastric cancer cells (P<0.001).The overexpression of SNRPD1 promoted the expression of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt) in gastric cancer cells (P=0.043,P<0.001),whereas disruption of SNRPD1 inhibited their expression (both P<0.001).Insulin-like growth factor 1,an agonist of the PI3K/Akt signaling pathway,promoted the proliferation of gastric cancer cells with SNRPD1 disturbed (P=0.002). Conclusion High expression of SNRPD1 in the gastric cancer tissues is associated with poor prognosis,and it may promote tumor cell proliferation and regulate the cell cycle by activating the PI3K/Akt signaling pathway.
gastric cancer / long-term prognosis / small nuclear ribonucleoprotein D1 / cell cycle / phosphatidylinositol 3-kinase/protein kinase B signaling pathway
| [1] |
The molecular mechanism of the significant role of long noncoding RNAs (lncRNAs) in the progression and metastasis of gastric cancer (GC) remains largely elusive. Our objective is to detect overexpressed lncRNA in GC and investigate its role in promoting epithelial-mesenchymal transition and tumour microenvironment remodel.LncRNA differential expression profile in GC was analysed using RNA microarrays. The level of LINC00501 was evaluated in both GC patient tissues and GC cell lines by quantitative reverse transcription PCR and large-scale (n = 304) tissue microarray. To explore the biological role and regulatory driver of LINC00501 in GC, various experimental techniques including Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) assay, dual luciferase assays were performed.Clinically, it was observed that LINC00501 level was abnormal overexpression in GC tissue and was associated with GC progression and distant metastasis. Gain and loss molecular biological experiments suggested that LINC00501, promoted EMT process and angiogenesis of GC. Mechanically, the enrichment of H3K27 acetylation in LINC00501 promoter region contributed to the increase of LINC00501 in GC. LINC00501 transactivated transcription of SLUG, by recruiting hnRNPR to its promoter. The growth of GC was inhibited both in vitro and in vivo by suppressing the level of LINC00501 using pharmacological intervention from the histone acetyltransferase (HAT) inhibitor -C646.This study suggests that LINC00501 promotes GC progression via hnRNPR/SLUG pathway, which indicates a promising biomarker and target for GC.© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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| [2] |
|
| [3] |
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| [4] |
There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied.A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS).The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC.The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.
|
| [5] |
张晓红, 李凡, 贝颂华, 等. CPNE家族在胃癌中的表达水平及其与患者预后的关系[J]. 国际消化病杂志, 2020, 40(6):377-383.DOI:10.3969/j.issn.1673-534X.2020.06.005.
|
| [6] |
|
| [7] |
Cancers harboring spliceosome mutations are highly sensitive to additional perturbations on the spliceosome that leads to the development of onco-therapeutics targeting the spliceosome and opens novel opportunities for managing aggressive tumors lacking effective treatment options such as triple negative breast cancers. Being the core spliceosome associated proteins, SNRPD1 and SNRPE have been both proposed as therapeutic targets for breast cancer management. Yet, their differences regarding their prognostic and therapeutic use as well as roles during carcinogenesis are largely unreported.We conducted in silico analysis at gene expression and genetic levels to differentiate the clinical relevance of SNRPD1 and SNRPE, and explored their differential functionalities and molecular mechanistic associations with cancer in vitro.We showed that high SNRPD1 gene expression was prognostic of poor breast cancer survival whereas SNRPE was not. The SNRPD1 expression quantitative trait loci, rs6733100, was found independently prognostic of breast cancer survival using TCGA data. Silencing either SNRPD1 or SNRPE independently suppressed the growth of breast cancer cells, but decreased migration was only observed in SNRPD1-silenced cells. Knocking down SNRPD1 but not SNRPE triggers doxorubicin resistance in triple negative breast cancer cells. Gene enrichment and network analyses revealed the dynamic regulatory role of SNRPD1 on cell cycle and genome stability, and the preventive role of SNRPE against cancer stemness that may neutralize its promotive role on cancer cell proliferation.Our results differentiated the functionalities of SNRPD1 and SNRPE at both prognostic and therapeutic levels, and preliminarily explained the driving mechanism that requires additional explorations and validations.© 2023. The Author(s).
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| [8] |
Precursor messenger RNA (pre-mRNA) splicing is catalyzed by an intricate ribonucleoprotein complex called the spliceosome. Although the spliceosome is considered to be general cell “housekeeping” machinery, mutations in core components of the spliceosome frequently correlate with cellor tissue-specific phenotypes and diseases. In this review, we expound the links between spliceosome mutations, aberrant splicing, and human cancers. Remarkably, spliceosome-targeted therapies (STTs) have become efficient anti-cancer strategies for cancer patients with splicing defects. We also highlight the links between spliceosome and immune signaling. Recent studies have shown that some spliceosome gene mutations can result in immune dysregulation and notable phenotypes due to missplicing of immune-related genes. Furthermore, several core spliceosome components harbor splicing-independent immune functions within the cell, expanding the functional repertoire of these diverse proteins. |
| [9] |
|
| [10] |
SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development.Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response.Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G/G stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression lost certain sensitivity to doxorubicin whereas luminal cancer cells did not.Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.
|
| [11] |
|
| [12] |
张鑫, 李迪诺, 田蕾, 等. 鼠尾草酸调节CXCR7/CXCL12轴对胃癌AGS细胞增殖、迁移和侵袭能力的影响[J]. 中国肿瘤生物治疗杂志, 2023, 30(8):695-700.DOI:10.3872/j.issn.1007-385x.2023.08.007.
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
郭梅, 王永兴. 川芎嗪对油酸诱导的大鼠急性肺损伤抗炎和稳定血管的作用[J]. 临床误诊误治, 2018, 31(12):80-86.DOI:10.3969/j.issn.1002-3429.2018.12.022.
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