scholarly journals Risk SNP-induced lncRNA-SLCC1 drives colorectal cancer through activating glycolysis signaling

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tingting Yan ◽  
Chaoqin Shen ◽  
Penglei Jiang ◽  
Chenyang Yu ◽  
Fangfang Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Patient Survival ◽  
Colorectal Carcinogenesis ◽  
Binding Motif ◽  
Poor Survival ◽  
Enhancer Activity ◽  
Glycolysis Pathway ◽  
Non Coding Rnas ◽  
Cancer Tissues

AbstractLong non-coding RNAs (lncRNAs) play key roles in colorectal carcinogenesis. Here, we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis. First, we identified rs6695584 as the causative SNP in 1q41 locus. The A>G mutation of rs6695584 created a protein-binding motif of BATF, altered the enhancer activity, and subsequently activated lncSLCC1 expression. Further validation in two independent CRC cohorts confirmed the upregulation of lncSLCC1 in CRC tissues, and revealed that increased lncSLCC1 expression was associated with poor survival in CRC patients. Mechanistically, lncRNA-SLCC1 interacted with AHR and transcriptionally activated HK2 expression, the crucial enzyme in glucose metabolism, thereby driving the glycolysis pathway and accelerating CRC tumor growth. The functional assays revealed that lncSLCC1 induced glycolysis activation and tumor growth in CRC mediated by HK2. In addition, HK2 was upregulated in colorectal cancer tissues and positively correlated with lncSLCC1 expression and patient survival. Taken together, our findings reveal a risk SNP-mediated oncogene lncRNA-SLCC1 promotes CRC through activating the glycolysis pathway.

scholarly journals Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 3947
Author(s):  
Dorota Zurawa-Janicka ◽  
Jarek Kobiela ◽  
Tomasz Slebioda ◽  
Rafal Peksa ◽  
Marcin Stanislawowski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Survival Data ◽  
Patient Survival ◽  
Mrna Level ◽  
Metastatic Potential ◽  
Colorectal Carcinogenesis ◽  
Cancer Tissue ◽  
Protein Levels ◽  
High Level

HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of HTRA1-3 was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the HTRA1 mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in HTRA1 and HTRA2 transcripts’ levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of HTRA1 and HTRA2 changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the HTRA1/2 genes’ expression are connected with metastatic potential of colorectal cancer and may affect patient survival.

scholarly journals Effects of pharmacological calcimimetics on colorectal cancer cells over-expressing the human calcium-sensing receptor

2020 ◽  
Author(s):  
Luca Iamartino ◽  
Taha Elajnaf ◽  
Katharina Gall ◽  
Jacquelina David ◽  
Teresa Manhardt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Tumor Growth ◽  
Colorectal Carcinogenesis ◽  
Inflammatory Factors ◽  
Type Ii ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

AbstractThe calcium-sensing receptor (CaSR) is a ubiquitously expressed multifunctional G protein-coupled receptor. Several studies reported that the CaSR plays an anti-inflammatory and anti-tumorigenic role in the intestine, and that it is down-regulated during colorectal carcinogenesis. We hypothesized that intestine-specific positive allosteric CaSR modulators (type II calcimimetics) could be used for the treatment of intestinal pathologies. Therefore, the aim of this study was to determine the effect of pharmacological stimulation of CaSR on gene expression in vitro and on tumor growth in vivo.We stably transduced two colon cancer cell lines (HT29 and Caco2) with lentiviral vectors containing either the CaSR fused to GFP or GFP only. Using RNA sequencing, RT-qPCR experiments and ELISA, we determined that CaSR over-expression itself had generally little effect on gene expression in these cells. However, treatment with 1μM of the calcimimetic NPS R-568 increased the expression of pro-inflammatory factors such as IL-23α and IL-8 and reduced the transcription of various differentiation markers in the cells over-expressing the CaSR. In vivo, neither the presence of the CaSR nor p.o. treatment of the animals with the calcimimetic cinacalcet affected tumor growth, tumor cell proliferation or tumor vascularization of murine HT29 xenografts.In summary, CaSR stimulation in CaSR over-expressing cells enhanced the expression of inflammatory markers in vitro, but was not able to repress colorectal cancer tumorigenicity in vivo. These findings suggest potential pro-inflammatory effects of the CaSR and type II calcimimetics in the intestine.

scholarly journals Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770365 ◽  
Author(s):  
Fangyuan Jing ◽  
Huicheng Jin ◽  
Yingying Mao ◽  
Yingjun Li ◽  
Ye Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profile ◽  
Colorectal Carcinogenesis ◽  
Rna Expression ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

scholarly journals Identification of Motile Sperm Domain Containing 1 (MOSPD1) As a Novel Target of the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

2021 ◽  
Author(s):  
Chiaki Horie ◽  
Chi Zhu ◽  
Kiyoshi Yamaguchi ◽  
Saya Nakagawa ◽  
Kiyoko Takane ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Regulatory Region ◽  
Motile Sperm ◽  
Enhancer Activity ◽  
Binding Motifs ◽  
Direct Target ◽  
Flanking Region ◽  
Novel Target ◽  
Cancer Tissues

Abstract Aberrant activation of the Wnt/β-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and we focused on MOSPD1, motile sperm domain containing 1, in this study. Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumorous cells of colorectal cancer tissues compared with non-tumorous cells. Using ChIP-seq data and JASPAR database, we searched for the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/β-catenin signaling, and identified a region containing three putative TCF-binding motifs in the 3’-flanking region. Additional analyses using reporter assay and ChIP-qPCR suggested that this region harbors an enhancer activity through an interaction with TCF7L2 and β-catenin. These data have clarified that MOSPD1 is a novel direct target of the Wnt/β-catenin signaling. In addition, the identification of its enhancer region may be helpful for the future studies of precise regulatory mechanisms of MOSPD1.

scholarly journals The component changes of lysophospholipid mediators in colorectal cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (5) ◽  
pp. 101042831984861 ◽  
Author(s):  
Chieko Kitamura ◽  
Hirofumi Sonoda ◽  
Hiroaki Nozawa ◽  
Kuniyuki Kano ◽  
Shigenobu Emoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Fatty Acid Analysis ◽  
Colorectal Carcinogenesis ◽  
Human Colorectal Cancer ◽  
Normal Tissues ◽  
Colon Cancers ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Cancer Tissues

Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography–tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.

Role of tumour- associated neutrophils in tissue material and systemic neutrophil inflammation in colorectal cancer patients

2021 ◽  
Vol 11 (2) ◽  
pp. 85-98
Author(s):  
K. Jakubowska ◽  
M. Koda ◽  
W. Kisielewski ◽  
K. Lomperta ◽  
M. Grudzińska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Distant Metastases ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues ◽  
Tumor Associated Neutrophils ◽  
Tissue Material

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Immune response is appear to be inseparable component of each part of tumorigenesis. Moreover, several studies have shown that some populations of neutrophils, called tumor-associated neutrophils (TANs) can be also actively involved in the tumor growth, anggenesis and development of the distant metastases in various cancer tissues.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

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