scholarly journals SMAD4–201 transcript as a putative biomarker in colorectal cancer

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Tamara Babic ◽  
Sandra Dragicevic ◽  
Marko Miladinov ◽  
Zoran Krivokapic ◽  
Aleksandra Nikolic

Abstract Background Transcripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4–201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods Relative abundance of SMAD4–201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results The relative abundance of SMAD4–201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4–201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4–202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4–201 and SMAD4–202. Conclusion The expression profile of SMAD4–201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan-ping Tang ◽  
Yi-xin Yin ◽  
Ming-zhi Xie ◽  
Xin-qiang Liang ◽  
Ji-lin Li ◽  
...  

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines.Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples.Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC.Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.


Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 606 ◽  
Author(s):  
Michele Astolfi ◽  
Giorgio Rispoli ◽  
Gabriele Anania ◽  
Veronica Nevoso ◽  
Elena Artioli ◽  
...  

Despite the great progress in screening techniques and medical treatments, colorectal cancer remains one of the most widespread cancers in both sexes, with a high death rate. In this work, the volatile compounds released from human colon cancer tissues were detected by a set of four different chemoresistive sensors, made with a nanostructured powder of metal-oxide materials, inserted into an innovative patented device. The sensor responses to the exhalation of a primary cancer sample and of a healthy sample (both of the same weight, collected during colorectal surgery from the intestine of the same patient) were statistically analyzed. The sensors gave reversible, reproducible, and fast responses for at least one year of continuous use, making them quite superior in respect to the existing diagnostic methods. Preliminary results obtained using principal component analysis of the sensor responses to samples removed from 13 patients indicate that the nanostructured sensors employed in this study were able to distinguish between healthy and tumor tissue samples with coherent responses (the discrimination power of the most sensitive sensor was about 17%), highlighting a strong potential for clinical practice.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e64961 ◽  
Author(s):  
Ana de la Cueva ◽  
Ana Ramírez de Molina ◽  
Néstor Álvarez-Ayerza ◽  
Ma Angeles Ramos ◽  
Arancha Cebrián ◽  
...  

2018 ◽  
Vol 49 (2) ◽  
pp. 545-554 ◽  
Author(s):  
Kaiming Wu ◽  
Jun Ma ◽  
Yanfeng Zhan ◽  
Kuanzhi Liu ◽  
Ziyin Ye ◽  
...  

Background/Aims: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood. Methods: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting. Results: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. Conclusion: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Dovile Dekaminaviciute ◽  
Rita Lasickiene ◽  
Seppo Parkkila ◽  
Vaida Jogaite ◽  
Jurgita Matuliene ◽  
...  

Carbonic anhydrases (CAs) are enzymes that catalyse the reversible hydration of CO2to bicarbonate. CA XII is considered a potential biomarker of tumor cells and a promising target for specific therapies. The aim of the current study was to develop new monoclonal antibodies (MAbs) against human recombinant CA XII and evaluate their diagnostic potential. An extracellular catalytic domain of human CA XII was expressed inE. coliand used as an immunogen. Seven stable hybridoma cell lines producing high-affinity IgG antibodies against human CA XII were generated. The majority of MAbs were highly specific to CA XII and did not cross-react with human recombinant CA I, CA II, CA VII, and CA XIII. In order to demonstrate the diagnostic value of the MAbs, they were employed for the immunohistochemistry analysis of CA XII expression in tissues. Two MAbs (15A4 and 4A6) demonstrated a strong and specific immunostaining of CA XII in human tissue specimens. Flow cytometry analysis of 5 human tumor cell lines with the MAb 15A4 revealed its immunoreactivity with cellular CA XII. In conclusion, the MAbs raised against recombinant catalytic domain of CA XII recognize cellular CA XII and represent a promising diagnostic tool for the immunodetection of CA XII-expressing cells.


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