DigitalUM :: Browsing by Subject "Gastric cancer"

Browsing by Subject "Gastric cancer"

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Open Access
ABRACL upregulated by transcription factor CBX4 promotes proliferation and migration and inhibits the apoptosis of gastric cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Guo, Kai; Gao, Xiao
Background. Gastric cancer (GC) is a predominant health concern in many countries. Actin-binding Rho activating C-terminal-like (ABRACL) belongs to a new family of low molecular weight proteins and has been implicated in cancers. This study was implemented to elucidate the role and mechanism of ABRACL in GC. Methods. The mRNA and protein expression of ABRACL and CBX4 in human gastric epithelium cell line GES-1 and GC cell lines was assessed with RT-qPCR and western blot. The transfection efficacy of sh-ABRACL, oe-CBX4, and sh-CBX4 was examined with RT-qPCR and western blot. AGS cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation assay, wound healing, and Transwell assays, respectively. With western blot analysis, flow cytometry, and caspase-3 assay kits, the expressions of MMP2 and MMP9, cell apoptosis, and caspase-3 activity were estimated. Western blot was adopted to estimate the contents of apoptosis-related proteins. Luciferase reporter and chromatin immunoprecipitation (ChIP) were applied to verify the interaction between ABRACL and CBX4. Results. The expression of ABRACL and CBX4 was increased in GC tissues and cells. After interfering with ABRACL, the proliferation, migration, and invasion of GC cells were inhibited while apoptosis was promoted. We also discovered that CBX4 could bind to ABRACL and transcriptionally regulate ABRACL expression in AGS cells. Rescue experiments revealed that CBX4 overexpression partially reversed the regulatory effects of ABRACL silencing on the proliferation, migration, invasion, and apoptosis of GC cells. Conclusion. Collectively, ABRACL transcriptionally upregulated by CBX4 promoted the malignant progression of GC.
Open Access
Analysis of HER2 status in gastroesophageal tumor specimens using a new automated HER2 IQFISH pharmDx™ (Dako Omnis) assay
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Viale, Giuseppe; Paterson, Jennifer; Bloch, Miriam; Csathy, George; Allen, David; Dell’Orto, Patrizia; Kjærsgaard, Gitte; Levy, Yaron Y.; Trøst Jørgensen, Jan
The human epidermal growth factor receptor 2 (HER2) is an important target for treatment of gastroesophageal cancer. Different slide-based assays are available for assessment of HER2 status. Overexpression of the HER2 protein is assessed by immunohistochemistry (IHC) whereas amplification of the HER2 gene is assessed by fluorescence in situ hybridization (FISH) or other in situ hybridization (ISH) methods. Here we report a summary of the validation data on HER2 IQFISH pharmDx™ (Dako Omnis), a newly developed assay for the automated staining platform Dako Omnis. This assay uses a non-toxic buffer that significantly reduces the hybridization time, which results in a total turnaround time of less than 4 hours from deparaffinization to counting of the gene and centromere signals. The data reported in the current summary cover method comparison, assessment of staining quality, observer-to-observer reproducibility as well as reproducibility within and between laboratories. Based on data from the different studies it was concluded that HER2 IQFISH pharmDx (Dako Omnis) is a reliable and robust assay, with high precision and at least comparable to the manual HER2 IQFISH pharmDx™ assay. The HER2 IQFISH pharmDx (Dako Omnis) assay is currently not commercially available outside the European Union.
Open Access
Circ_0000467 regulates proliferation, migration, invasion, and apoptosis in gastric cancer by targeting the miR-622/ROCK2 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Tan, Shengquan; Hu, Lingbo; Lei, Rui; Wang, Ruo; Chen, Jiaquan
Background. Gastric cancer (GC) ranks fourth as a cause of cancer-induced mortality worldwide. Recently, some studies have demonstrated that circular RNAs (circRNAs) play vital roles in human cancers, including GC. Methods. The expression levels of circ_0000467, microRNA-622 (miR-622), and Rho-associated coiledcoil-containing protein kinase2 (ROCK2) were determined by RT-qPCR assay. The protein expression was quantified by western blot assay. The interaction relationship between miR-622 and circ_0000467 or ROCK2 was confirmed by dual-luciferase reporter assay and RIP assay. The biological behaviors of GC cells including proliferation, apoptosis, migration, and invasion were determined by EdU assay, colony-forming assay, flow cytometry, and transwell assay. The effects of circ_0000467 silencing in vivo were assessed by a xenograft experiment in nude mice. Results. MiR-622 was downregulated and ROCK2 was upregulated in GC tissues and cells. Loss-offunction experiment revealed that overexpression of miR-622 decreased proliferation, migration, and invasion while it increased apoptosis in GC cells. Furthermore, ROCK2 was a functional target of miR622, and upregulation of ROCK2 abolished miR-622- induced effects on GC cells. What’s more, circ_0000467 was upregulated in GC, and inhibition of miR-622 reversed silencing of circ_0000467-caused effects on GC cells, suggesting that miR-622 was a target of circ_0000467. The suppression of circ_0000467 was able to slow the tumor growth in vivo. Conclusion. Mechanistically, circ_0000467 functioned as an oncogenic regulator in GC by specifically binding to miR-622 to upregulate ROCK2, which might be novel diagnostic markers for GC.
Open Access
CircAKT3 promotes cell proliferation, survival and glutamine metabolism of gastric cancer by activating SLC1A5 expression via targeting miR-515-5p
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Li, Fei; Zhang, Lixiao; Sun, Qi
Background. Gastric cancer (GC) is a common disorder in the population. Numerous studies have reported that the pathogenesis of GC is implicated in the dysregulation of circular RNAs (circRNAs). The aim of this study was to investigate the role and functional mechanism of circ_0000199 (circAKT3) in GC. Methods. The expression of circAKT3, miR-515-5p and solute carrier family 1 member 5 (SLC1A5) mRNA was measured by quantitative real-time PCR (qPCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2'- deoxyuridine (EdU) assay. Cell apoptosis was determined by flow cytometry assay and caspase 3/7 activity. The protein levels of glutaminase (GLS), proliferating cell nuclear antigen (PCNA) and cleavedcaspase3 were detected by western blot. The binding relationship between miR-515-5p and circAKT3 or SLC1A5 was verified by dual-luciferase reporter assay or RIP assay. The role of circAKT3 in vivo was investigated by establishing animal models. The abundance of Ki-67 and PCNA was detected by IHC assay. Results. The expression of circAKT3 in GC tissues and cells was enhanced. The knockdown of circAKT3 inhibited GC cell proliferation, survival and glutamine metabolism, as well as tumor growth in animal models. MiR-515-5p was a target of circAKT3, and miR-515-5p suppressed the expression of SLC1A5 by binding to SLC1A5 3'UTR. CircAKT3 relieved the inhibition of miR-515-5p on SLC1A5 expression by targeting miR515-5p. The effects of circAKT3 knockdown were reversed by miR-515-5p depletion, and the effects of miR-515-5p restoration were abolished by SLC1A5 overexpression. Conclusion. CircAKT3 promotes the malignant development of GC by activating SLC1A5 expression via targeting miR-515-5p.
Open Access
Circular RNA circLRCH3 promotes oxaliplatin resistance in gastric cancer through the modulation of the miR-383-5p/FGF7 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xiang, Chengcheng; Li, Rong; Qiu, Huizhu; Zuo, Erdong; Zhang, Yuan; Shan, Li; Cheng, Xu
Background. Gastric cancer (GC) is a common malignant tumor of the digestive system. Circular RNAs (circRNAs) play a vital role in tumorigenesis and chemoresistance. The current study aimed to explore the possible role and mechanism of circRNA leucine rich repeats and calponin homology domain containing 3 (circLRCH3) in GC chemoresistance. Methods. The levels of circLRCH3, microRNA-3835p (miR-383-5p) and fibroblast growth factor 7 (FGF7) were determined by quantitative real-time PCR or Western blot. Cell Counting Kit-8 (CCK-8) assay was utilized to evaluate cell survival rate and proliferation ability. Colony formation, transwell and flow cytometry assays were used to assess cell proliferation, migration, invasion and apoptosis. The expression of multidrug resistance proteins was detected by Western blot. The binding relationship between miR-383-5p and circLRCH3/FGF7 was verified by dual-luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the role of circLRCH3 in OXA resistance in vivo. Results. CircLRCH3 and FGF7 levels were upregulated, while miR-383-5p level was reduced in OXAresistant GC tissues and cells. Depletion of circLRCH3 attenuated the resistance of OXA-resistant cells to OXA. CircLRCH3 silence reduced OXA resistance by regulating miR-383-5p. Besides, miR-383-5p elevated OXA sensitivity of GC cells by repressing FGF7. Moreover, the deletion of circLRCH3 increased OXA sensitivity in vivo. Conclusions. Knockdown of circLRCH3 alleviated OXA resistance of GC by modulating the miR-3835p/FGF7 axis, which provided a promising therapeutic target for GC chemoresistance.
Open Access
Clinicopathological features and lymph node metastatic patterns of gastric mixed adenoneuroendocrine carcinoma
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Chen, Hanrui; Shu, Man; Chen, Sile; Xue, Ling; Linn, Yua
Aims. Mixed adenoneuroendocrine carcinoma (MANEC), also known as high- grade mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the World Health Organization (WHO) classification of tumors of the endocrine organs (2017), is a rare gastric malignancy. Here, we present 10 cases of gastric MANEC and analyse their clinicopathological features and lymph node metastatic patterns. Methods and results. Six patients were male, and four were female. The mean age of the patients was 67.9 years. Grossly, most tumors presented as ulcerative mass, located in gastric fundus or/and cardia. Microscopically, the neuroendocrine component, large cell neuroendocrine carcinoma in most cases (8/10), constituted 30-70% of the whole tumor. It was diffusely positive for CD56 or/and synaptophysin in all cases, but negative for chromogranin A in 9 cases. Ki-67 index was 50-80% in neuroendocrine component. The glandular component was moderately (6/10) or poorly (4/10) differentiated adenocarcinoma. Nine of 10 cases were positive for lymph node metastasis, with pure neuroendocrine component (6/9), or pure glandular component (1/9), or mixed components (2/9). The patients were treated with surgery, combining with chemotherapy (4/10), radiotherapy (2/10) and immunotherapy (1/10). Five patients died from tumor progress, with an average survival time of 18.6 months. The dead cases had predominant neuroendocrine component in primary tumor or in metastatic lymph nodes. Conclusions. Neuroendocrine component may determine the clinical behavior and outcome in gastric MANEC. Different metastatic component makes the selection of chemotherapy protocol more challenging.
Open Access
CRISPR-mediated WNK4 point mutation aggravates tumor progression and weakens chemotherapy sensitivity in gastric cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ying, Xiaojun; Ying, Zhen; Gao, Xiaobing; Wang, Yong; Lv, Xinting
Objective. Gastric cancer (GC) is the fifth most common malignancy, the molecular targets of which have been increasingly explored in recent years. As a serine/threonine protein kinase, the role of WNK lysine deficient protein kinase 4 (WNK4) in GC was clarified in this study. Methods. Human GC lines AGS and MKN45 were stably transfected with a WNK4 mutant constructed by the CRISPR/Cas9 method and treated with cis-dichlorodiammine platinum (CDDP, 2 μg/mL) and 5-fluorouracil (5-FU, 5 μg/mL) for 48h. Tumor-bearing mice were established with 5×106 mutant-type AGS cells, and injected with 40 mg/kg WP1066, the inhibitor of signal transducer and activator of transcription 3 (STAT3), for 21 days. Cell malignant potential and tumor growth were assessed. STAT3 activation was identified by western blot and immunohistochemistry. The interaction between WNK4 and STAT3 was determined using co-immunoprecipitation and immunofluorescence co-localization. Results. WNK4 mutation promoted proliferation and invasion, and upregulated the p-STAT3/STAT3 value in GC cells with/without 5-FU and CDDP treatments, while inhibiting apoptosis of GC cells without drug treatment. In tumor-bearing mice, WNK4 mutation accelerated tumor growth, increased levels of p-STAT3, STAT3, and p-STAT3/STAT3, and strengthened the co-immunoprecipitation and co-localizing with STAT3; however, these effects were reversed by WP1066 treatment. Conclusion. Through activating STAT3, WNK4 mutation impacts both the natural and drug-treated growth of GC cells or tumors, suggesting a new avenue for preclinical research.
Open Access
Diameter of involved nerves is a valuable prognostic factor for gastric cancer
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Zhou, Zhi-hua; Zhang, Jian-dong; Zhao, Hai-Bin; Wu, Yao-yi
The prognostic role of perineural invasion (PNI) in gastric cancer remains unclear. We hypothesized that the diameter of the tumor-involved nerves might be a useful indicator for prognosis. By labeling nerves and cancer cells in 204 cases of gastric cancer with single or double immunochemistry, we found that 146 cases were PNI positive and that 58 were PNI negative. For each case with PNI, the maximum diameter of the involved nerve was measured microscopically. Then, we correlated this parameter with the patients’ 5-year overall survival, and receiver operating curves were used to determine the cutoff value. We found that the optimal cutoff value for predicting 5-year survival was 65 µm (sensitivity 76.9%, specificity 70.0%). Next, all 204 patients were classified into two groups as follows: Group A, PNI-positive cases in which the largest involved nerves were ≥65 µm in diameter (110 cases); Group B, PNI-positive cases in which the largest involved nerves were <65 µm and all PNI-negative cases (94 cases). Compared with Group A, Group B had a better 5-year survival (74.5% vs 27.3%) and a better 5-year disease-free survival (63.8% vs 23.6%). Multivariate analysis suggested that a ≥65 µm maximum diameter of the involved nerves was an independent risk factor for both recurrence (P<0.001) and gastric cancer-related death (P<0.001) within 5 years. However, if all patients were classified simply based on whether PNI existed (regardless of the nerve size), this did not provide more information than traditional clinicopathological variables. In conclusion, the presence of cancer-involved nerves with a diameter ≥65 µm was a valuable prognostic factor for gastric cancer.
Open Access
Editorial: Diet and digestive tract cancers: investigating the nutritional influences on gastrointestinal carcinogenesis
(Frontiers Media, 2025-11-06) Huerta Castaño, José María; Colorado Yohar, Sandra Milena; Salmerón Martínez, Diego; Armando Agudelo, Nelson; Ciencias Sociosanitarias; Facultad de Medicina
Open Access
EFNA4 deletion suppresses the migration, invasion, stemness, and angiogenesis of gastric cancer cells through the inactivation of Pygo2/Wnt signaling
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Xian; Zhang, Tiran; Yu, Rong
Gastric cancer represents an aggressive malignancy and a leading contributor to cancer death. Ephrin-A4 (EFNA4) has been proposed to be related to the immune microenvironment and prognosis of gastric cancer. This study was undertaken to discuss the participation and mechanism of EFNA4 in the development of gastric cancer. RT-qPCR and western blot examined EFNA4 and Pygopus2 (Pygo2) expression in gastric cancer cells. After transfection of EFNA4 interference plasmids or co-transfection of EFNA4 interference plasmids and Pygo2 overexpression plasmids, cell proliferation was detected by the CCK-8 method and EDU staining. Wound healing, Transwell, TUNEL, and endothelial cell tube formation assays detected cell migration, invasion, apoptosis, and angiogenesis, respectively. Western blot examined the expression of metastasis-, apoptosis-, angiogenesis-, and Wnt signaling-associated proteins. Cell stemness was estimated by the sphere formation assay, RT-qPCR, and western blot. Through the experimental data, it was noticed that EFNA4 expression was increased in gastric cancer cells. Knockdown of EFNA4 suppressed the proliferation, migration, invasion, angiogenesis as well as stemness while aggravating the apoptosis of gastric cancer cells. Also, EFNA4 depletion reduced Pygo2 protein expression and then inactivated Wnt/β-catenin signaling. Further elevation of Pygo2 reversed the impacts of EFNA4 silencing on Wnt/β-catenin signaling, cell proliferation, apoptosis, migration, invasion, angiogenesis as well as stemness in gastric cancer. Accordingly, the knockdown of EFNA4 might downregulate Pygo2 and inactivate Wnt/β-catenin signaling to exert protective effects against gastric cancer
Open Access
Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion
(2026) Hao Shang; Xiali Shi; Hanmei Jiang; Ji Di; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Background. Gastric cancer (GC) seriously affects the life and health of patients, and the role of Elp3 in GC is still unclear; therefore, the aim of this study was to investigate the role and mechanism of Elp3 overexpression in GC. Methods. Elp3-overexpressing HGC27 cells were constructed with an overexpression plasmid, and Elp3 overexpressing GC nude mice were prepared, which were intervened by histone acetylation inhibitor (SAHA) or JNK pathway inhibitor (SP600125). The protein interactions between Elp3 and JNK1 were verified by Co-immunoprecipitation (Co-IP) assay. Cell prolifera tion, migration, invasion, JNK/MAPK pathway, and histopathological changes were evaluated with CCK-8, clone formation assay, scratch assay, Transwell, qRT PCR, western blot, and HE staining. Results. Elp3 interacted with JNK1 protein, and Elp3 overexpression promoted GC proliferation, invasion, migration, elevated HAT activity, and activation of the JNK/MAPK pathway. A histone acetylation inhibitor attenuated the promotional effect of Elp3 overexpression on GC and activation of the JNK/MAPK pathway. Further, inhibition of the JNK/MAPK pathway also suppressed the promotion of GC by Elp3 overexpression. Conclusion. Elp3 may be involved in GC progression by activating the JNK/MAPK pathway through histone acetylation.
Open Access
Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract
(Murcia : F. Hernández, 2004) Kayed, Hany; Kleeff, Jörg; Ding, J.; Hammer, J.; Giese, T.; Zentgraf, H.; Büchler, M.W.; Friess, Helmut
Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-ß on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-ß down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.
Open Access
Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression
(Murcia : F. Hernández, 2009) Lee, Soo Han; Kang, Hyun Jeong; Shin, Dong-Hun; Cho, Duk-Yeon; Song, Jin Mi; Kim, G.H.; Song, G.A.; So, Mee Young; Kim, J.Y.; Choi, K.U.; Lee, Chian-Her; Huh, G.Y.; Park, D.Y.; Lee, H.C.
The biological characteristics of intestinaltype early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of betacatenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and betacatenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs.
Open Access
Expression of claudin-2 in the multistage process of gastric carcinogenesis
(Murcia : F. Hernández, 2008) Song, X.; Li, X.; Tang, Y.; Chen, H.; Wong, B.; Wang, J.; Chen, M.
Objective: Claudin-2 is an important component of the tight junction (TJ) of epithelial cells, and its protein expression between many tumours is significantly different. It is unclear if Claudin-2 overexpression is a trigger or a consequence during carcinogenesis. The multistage tissues of gastric carcinogenesis provides us a valuable model for determining tumourigenicity. Methods: This paper investigated, for the first time, claudin-2 expression in the pathological paraffin tissues of sinus ventriculi from gastroscopic biopsy. To determine claudin-2 expression in gastric carcinogenesis by immunochemical ABC technique. Results: Altogether, 108 chronic superficial gastritis, 55 chronic atrophic gastritis, 109 intestinal-type metaplasia, 93 dysplasia and 52 gastric intestinal-type adenocarcinoma samples were analyzed. Results indicated that the percentage of claudin-2-positive cases was 0% for chronic superficial gastritis (0/108), 0% for chronic atrophic gastritis (0/55), 0% for intestinal-type metaplasia (0/109), 35.87% for dysplasia (33/92), and 73.47% for gastric intestinal-type adenocarcinoma (36/49) respectively, primarily in the cell membrane, and gradually increased in the multistage process of gastric carcinogenesis (P<0.001). Conclusions: This suggests that claudin-2 protein overexpression may be closely correlated to gastric carcinogenesis.
Open Access
Expression of matrix metalloproteinases MMP-2 and MMP-9 in gastric cancer and their relation to claudin-4 expression
(Murcia : F. Hernández, 2008) Lee, Li-Yu; Wu, Chi-Ming; Wang, Chee-Chan; Yu, Jau-Song; Liang, Ying; Huang, Kuo-Hao; Lo, Chih-Hong; Hwang, Tsann-Long
Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. Claudin-4 has been shown to activate MMP-2, indicating that claudin-mediated increased cancer cell invasion might be mediated through the activation of MMP proteins. To explore the roles of MMP-2, MMP-9 and claudin-4 in gastric cancer, we selected 88 cases and then analyzed the expression of these proteins using immunohistochemistry. We found that all of MMP-2, MMP-9 and claudin-4 expressions were significantly higher in intestinal-type than in diffuse-type gastric cancer. On further analysis, testing the relationship between MMP-2 and MMP-9 expression with claudin-4 expression, claudin-4 expression was significantly associated with MMP-9 expression, but not with MMP-2 expression. The results showed that MMP- 2, MMP-9 and claudin-4 expression may be phenotypic features, distinguishing intestinal-type and diffuse-type gastric cancer. Possibly, claudin-4 played a role in determining MMP-9 activity which favored intestinaltype gastric cancer to distal metastasis.
Open Access
Gastric cancer preceeded by severe dysplasia
(Murcia : F. Hernández, 1986) Takeo Nagayo
For elucidation of histogenesis of gastric cancer derived from relatively flat mucosa, 77 cases of surgically resected stomachs with lesions of severe dysplasia in cancerous mucosae or with cancerous changes in severely dysplastic mucosae were detected out of 380 recently examined cases of early gastric cancer. Several examples of early gastric cancer of the superficial type, showing histological changes indicating that they had developed on the preexisted dysplastic mucosal lesions, have been presented, together with the background data. The frequency for detecting such changes was higher in the slightly elevated lesions than in the depressed or eroded ones.
Open Access
Genetic and epigenetic alterations of tumor suppressor and tumor-related genes in gastric cancer
(Murcia : F. Hernández, 2002) Tamura, G.
Both genetic and epigenetic alterations of tumor suppressor and tumor-related genes involved in the pathogenesis of gastric cancer are reviewed here, and molecular pathways of gastric carcinogenesis are proposed. Gastric carcinomas are believed to evolve from native gastric mucosa or intestinal metaplastic mucosa that undergoes genetic and epigenetic alterations involving either the suppressor pathway (defects in tumor suppressor genes) or mutator pathway (defects in DNA mismatch repair genes). Methylation of E - c a d h e r i n in native gastric mucosa results in undifferentiated carcinomas (suppressor pathway), while methylation of hMLH1 results in differentiated foveolartype carcinomas (mutator pathway). The majority of d i fferentiated gastric carcinomas however, arise from intestinal metaplastic mucosa and exhibit structural alterations of tumor suppressor genes, especially p 5 3. They appear to be related to chronic injury, perhaps due to Helicobacter pylori infection. Approximately 20% of differentiated carcinomas (ordinary-type) have evidence of mutator pathway tumorigenesis. Mutations of E - c a d h e r i n are mainly involved in the progression of d i fferentiated carcinomas to undifferentiated tumors. The molecular pathways of gastric carcinogenesis depend on the histological background, and gastric carcinomas show distinct biological behaviors as a result of discernible cellular genetic and epigenetic alterations.
Open Access
Hsa_circ_0026344 suppresses gastric cancer progression via modulating the miR-1290/FBP2 axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xiao, GaoChun; Zhang, TingTing; Tan, BinBin; Hao, Hu
Background. Circular RNAs (circRNAs) are a novel type of noncoding RNAs and play important roles in tumorigenesis, including gastric cancer (GC). However, the functions of most circRNAs remain poorly understood. In our study, we mainly learn the influence of hsa_circ_0026344 (circ_0026344) in GC progression. Methods. Circ_0026344, miR-1290 and Fructose1,6-bisphosphatase 2 (FBP2) expression was determined by quantitative real-time polymerase chain reaction (qRT-PCR). GC cell proliferation, migration, and invasion were detected by colony formation, 5-ethynyl2’-deoxyuridine (EdU), and transwell assays, respectively. The interaction between circ_0026344 and miR-1290 complex was evaluated by RNA pull-down assay. The interaction of miR-1290 with circ_0026344 or FBP2 was detected using dual-luciferase reporter assay. A xenograft model was established to determine the effect of circ_0026344 on GC tumor growth in vivo. Results. Circ_0026344 expression was dramatically decreased in GC cells and tissues. Circ_0026344 overexpression inhibited GC cell proliferation, migration and invasion. MiR-1290 was predicted as a target of circ_0026344 and miR-1290 overexpression attenuated the anti-tumor effect of circ_0026344 on GC cells. Furthermore, we predicted FBP2 as the target of miR1290. FBP2 knockdown reversed the effects of circ_0026344 knockdown on GC cell malignant behaviors. Functional analysis showed that circ_0026344 upregulated FBP2 expression via miR1290. Additionally, in vivo studies demonstrated that circ_0026344 suppressed GC tumor progression. Conclusion. In conclusion, circ_0026344 inhibited GC cell proliferation via the miR-1290/FBP2 axis, which might provide a new therapeutic target for GC patients.
Open Access
Involvement of lncRNA dysregulation in gastric cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Sun, Ming; Nie, Feng-qi; Wang, Zhao-xia; De, Wei
y. Benefiting from the fast development of sequencing technique and bioinformatics methods, more and more new long non-coding RNAs (lncRNAs) are discovered and identified. lncRNAs were firstly thought to be transcription noise that from genome desert without biological function; however, as the discovery of lncRNA XIST and HOTAIR uncovers the emerging roles of lncRNAs in development and tumorigenesis. In the past decades, accumulating evidence have indicated that lncRNAs involve in a wide range of biological functions, such as X-chromosome inactivation, reprogramming stem cell pluripotency, regulation of the immune response and carcinogenesis. Although lots of studies have demonstrated that dysregulation of lncRNAs involve in diverse diseases including cancers, the underlying molecular mechanisms of lncRNAs are not well documented. Interestingly, our previous studies and others’ have shown that numerous of lncRNAs expression was misregulated in gastric cancer. In this review, we will focus on the dysregulated lncRNAs and their biological function and underlying pathways or mechanisms in GC. Finally, we will discuss the potential roles of lncRNAs acting as biomarkers or therapeutic targets in GC patients.
Open Access
Knockdown of kinesin family member 2C restricts cell proliferation and induces cell cycle arrest in gastric cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Li, Shuai; Ma, Yulian; Wu, Chen; Hou, Xinfang
Kinesin family member 2C (KIF2C) was reported to act as a vital player in several human cancers. However, the exact function of KIF2C in gastric cancer (GC) is poorly understood. In the present study, the potential role of KIF2C was studied in gastric cancer by bioinformatics analysis and proliferation assay. KIF2C expression was detected using reverse transcription-quantitative polymerase chain reaction and western blot. Our data showed that the expression of KIF2C was increased in different tumor tissues, including GC. KIF2C was overexpressed in GC tissues and might be used as a diagnostic and prognostic biomarker for GC. KIF2C expression was correlated with immune infiltration and the levels of cell cyclerelated genes in GC. Moreover, silencing of KIF2C can cause cell cycle arrest, and inhibit the proliferative ability of GC cells. Thus, our studies revealed that KIF2C levels might serve as a promising biomarker for diagnosis and prediction of prognosis of GC, and targeting KIF2C might be an effective therapeutic strategy for GC.