Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer

Pavlovic, Mladen; Gajovic, Nevena; Jurišević, Milena; Mitrović, Slobodanka; Radosavljević, Gordana; Pantic, Jelena; Arsenijević, Nebojša; Jovanović, Ivan

doi:10.1155/2018/6578273

“…This result was consistent with our findings that NDUFA4 was highly expressed in GC and correlated with the poor prognosis of GC patients. Gastric adenocarcinoma is histologically divided into intestinal, diffuse, mixed, and indeterminate subtypes, whereas the diffuse type of GC usually has a shorter duration of disease and poor prognosis [ 27 ]. Our results have revealed that NDUFA4 was highly expressed in all HER2-negative GC cell lines compared with normal human gastric epithelium, in which intestinal-type GC cell lines (MKN28, AGS) showed higher NDUFA4 expression in comparison to intestinal diffuse-type GC cell lines (MKN45).…”

Section: Discussionmentioning

confidence: 99%

m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer

Xu

¹

,

Lai

²

,

Pan

³

et al. 2022

View full text Add to dashboard Cite

Gastric cancer (GC) is a malignancy with poor prognosis. NDUFA4 is reported to correlate with the progression of GC. However, its underlying mechanism in GC is unknown. Our study was to reveal the pathogenic mechanism of NDUFA4 in GC. NDUFA4 expression was explored in single-cell and bulk RNA-seq data as well as GC tissue microarray. Mitochondrial respiration and glycolysis were estimated by oxygen consumption rate and extracellular acidification rate, respectively. The interaction between NDUFA4 and METTL3 was validated by RNA immunoprecipitation. Flow cytometry was used to estimate cell cycle, apoptosis and mitochondrial activities. NDUFA4 was highly expressed in GC and its high expression indicated a poor prognosis. The knockdown of NDUFA4 could reduce cell proliferation and inhibit tumor growth. Meanwhile, NDUFA4 could promote glycolytic and oxidative metabolism in GC cells, whereas the inhibition of glycolysis suppressed the proliferation and tumor growth of GC. Besides, NDUFA4 inhibited ROS level and promoted MMP level in GC cells, whereas the inhibition of mitochondrial fission could reverse NDUFA4-induced glycolytic and oxidative metabolism and tumor growth of GC. Additionally, METTL3 could increase the m6A level of NDUFA4 mRNA via the m6A reader IGF2BP1 to promote NDUFA4 expression in GC cells. Our study revealed that NDUFA4 was increased by m6A methylation and could promote GC development via enhancing cell glycolysis and mitochondrial fission. NDUFA4 was a potential target for GC treatment.

show abstract

“…IL-32 is mainly produced by activated T cells, NK cells, epithelial cells, and blood monocytes ( 7 ), and it has nine splice variants IL-32 α , IL-32 β , IL-32 γ , IL-32 δ , IL-32 ε , IL-32 θ , IL-32 ζ , IL-32 η , and IL-32small (IL-32sm) ( 8 , 9 ). IL-32 has been implicated in many inflammatory diseases and cancers, including rheumatoid arthritis ( 10 ), chronic obstructive pulmonary disease (COPD) ( 11 ), lymphoma ( 12 ), head and neck squamous cell carcinoma (HNSCC) ( 13 ), thyroid cancer (TC) ( 14 ), hepatocellular carcinoma (HCC) ( 15 ), lung cancer (LC) ( 16 – 18 ), esophageal cancer ( 19 ), gastric cancer (GC) ( 20 , 21 ), pancreatic cancer ( 22 ), colorectal cancer (CRC) ( 23 , 24 ), renal cell carcinoma (RCC) ( 25 ), breast cancer ( 26 ), and endometrial cancer (EC) ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Associations between Interleukin-32 Gene Polymorphisms rs12934561 and rs28372698 and Susceptibilities to Bladder Cancer and the Prognosis in Chinese Han Population

Yang

¹

,

Jian

²

,

Shen

³

et al. 2020

View full text Add to dashboard Cite

The proinflammatory chemokine interleukin-32 is related to various diseases, including cancer. However, it has never been associated with bladder cancer (BC). To detect whether there is a relationship between the IL-32 gene polymorphisms (rs12934561 C/T and rs28372698 T/A) and BC, the study enrolled 170 non-muscle-invasive bladder cancer (NMIBC) patients, 151 muscle-invasive bladder cancer (MIBC) patients, and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the IL-32 single-nucleotide polymorphism (SNP) genotyping. Statistical analysis was performed using SNPstats online analysis software and SPSS software. Our data revealed that the CC homozygous genotype of rs12934561 in BC patients was significantly higher than that in controls ( P = 0.03 , OR = 1.47 , 95 % CI = 1.04 ‐ 2.08 ), and the percentage of TC genotype carriers was relatively less than that of controls ( P = 0.001 , OR = 0.61 , 95 % CI = 0.45 ‐ 0.82 ). Furthermore, the TT homozygous genotype of rs28372698 was associated with a significantly lower overall survival rate in MIBC patients ( P = 0.028 , OR = 2.77 , 95 % CI = 1.11 ‐ 6.90 ). The IL-32 gene polymorphism rs12934561 might be associated with increased BC risk, and the rs28372698 might participate in the prognosis of BC patients. Therefore, they could be potential forecasting factors for the prognosis of MIBC patients.

show abstract

“…However, in patients with a more aggressive diffuse type of GC, there was a decrease in the expression of MVD in the tumor compared with GC of the intestinal type, and this decrease was associated with advanced TNM stage of the disease. There were no differences in VEGF expression in GC of diffuse and intestinal types[ 162 ].…”

Section: Results Of Angiogenesis Activity Assessment In Gcmentioning

confidence: 99%

Issues of origin, morphology and clinical significance of tumor microvessels in gastric cancer

Сеньчукова¹

2021

WJG

View full text Add to dashboard Cite

Gastric cancer (GC) remains a serious oncological problem, ranking third in the structure of mortality from malignant neoplasms. Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers. It is known that the main cause of death from malignant neoplasms and GC, in particular, is tumor metastasis. Given that angiogenesis is a critical process for tumor growth and metastasis, it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy. In the presented review, modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered; data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized; and various approaches to the classification of tumor vessels, as well as the methods for assessing angiogenesis activity in a tumor, are highlighted. Here, results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed, and a new classification of tumor microvessels in GC, based on their morphology and clinical significance, is proposed for consideration.

show abstract

Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer

Cited by 6 publications

References 47 publications

m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer

m6A RNA methylation-mediated NDUFA4 promotes cell proliferation and metabolism in gastric cancer

Associations between Interleukin-32 Gene Polymorphisms rs12934561 and rs28372698 and Susceptibilities to Bladder Cancer and the Prognosis in Chinese Han Population

Issues of origin, morphology and clinical significance of tumor microvessels in gastric cancer

Contact Info

Product

Resources

About