The Diagnostic Efficacy and Biological Effects of microRNA-29b for Colon Cancer

Background: Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study. Methods: There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels. Results: It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration. Conclusion: In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.

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Long Non-Coding RNA-Colon Cancer Associated Transcript 1 Down-Regulation Inhibits Cell Proliferation and Promotes Apoptosis in Colorectal Cancer Through Enhancing miR-152 Expression

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2491 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1766-1772

Author(s):

Jindong Li ◽

Xi Wang ◽

Xin Huang ◽

Na Li ◽

Ya Ling ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Viability ◽

Cancer Cell ◽

Cancer Progression ◽

Biological Effects ◽

Colorectal Cancer Cell ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Cancer Tissue ◽

Colorectal Cancer Progression

Colorectal cancer is a common malignant cancer that is characterized by high mortality rate. CCAT1 is a type of newly discovered lncRNA. This research was conducted to study the role of CCAT1 in colorectal cancer. The findings showed that there was significant up-regulation of CCAT1 expression in colorectal cancer. Then, online bioinformatic database and dual-luciferase reporter assay to prove CCAT1 and miR-152 have direct binding sites. Many researches demonstrated that miR-152 played a crucial role in development of colorectal cancer. Therefore, we then explored the relationship between CCAT1 and miR-152 in colorectal cancer. qRT-PCR analysis showed that miR-152 was lowly expressed in cancer tissue and cells. We then explored the effect of CCAT1 and miR-152 on the biological effects of colorectal cancer cells. MiR-152 up-regulation significantly reduced colorectal cancer cell viability and enhanced apoptosis. Furthermore, CCAT1-shRNA inhibited colorectal cancer cell viability and enhanced cell apoptosis were significantly eliminated by miR-152 inhibitor. Combined with all results, CCAT1/miR-152 axis was related to colorectal cancer progression regulation, which might be used as new therapeutic targets for colorectal cancer treatment.

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Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

International Journal of Molecular Sciences ◽

10.3390/ijms22168470 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8470

Author(s):

Hui Wang ◽

Tian Tian ◽

Jinhua Zhang

Keyword(s):

Colorectal Cancer ◽

Clinical Care ◽

Inflammatory Cells ◽

Genetic Alterations ◽

Tumor Associated Macrophages ◽

Invasion And Migration ◽

Complex Process ◽

Incidence And Mortality ◽

And Migration

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.

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WNT7A Overexpression Inhibits Growth and Migration of Hepatocellular Carcinoma via the β-Catenin Independent Pathway

BioMed Research International ◽

10.1155/2019/3605950 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Lihui Lan ◽

Wei Wang ◽

Yue Huang ◽

Chenghai Zhao ◽

Xianmin Bu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Viability ◽

Caspase 3 ◽

Clinical Information ◽

Transcriptional Factor ◽

Biological Behavior ◽

Cancer Tissue ◽

Expression Data ◽

Digestive Cancer ◽

And Migration

Background/Aims. Hepatocellular carcinoma (HCC) is the lethal digestive cancer and the second leading cause of cancer death in men worldwide. Wnt7a, a 39Kd secreted glycoprotein composed of 349 amino acids, was reported to be related to various diseases. However, its role in HCC has not been studied yet. In this study, using gene expression data and clinical information obtained from the Oncomine and KMplot database, we acknowledged that WNT7A was underexpressed in HCC cancer tissue compared with normal tissue, and WNT7A underexpression was correlated with the decreased survival rate of HCC patients. The function of Wnt7a in cell viability, apoptosis, and migration was evaluated by biological behavior assay and molecular analysis. The findings revealed that WNT7A overexpression significantly restrained cell viability and migration while enhancing apoptosis. In addition, WNT7A overexpression promoted cell apoptosis by strengthening Caspase-3 activity and inhibited migration by downregulating EMT transcriptional factor Snail. Furthermore, the expression level of SKP2 was significantly downregulating in the WNT7A overexpression group. In conclusion, this study illustrated that overexpression of WNT7A inhibited cell viability and migration, which was likely attributed to the regulation of SKP2/P21.

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A VIEW ON THE PROBLEM OF INADEQUATE SCREENING OF COLORECTAL CANCER IN UKRAINE

Likarska sprava ◽

10.31640/jvd.3.2019(1) ◽

2019 ◽

pp. 3-5

Author(s):

Nelya Melnitchouk ◽

Galyna Shabat

Keyword(s):

Colorectal Cancer ◽

Clinical Symptoms ◽

Screening Program ◽

Early Stage ◽

Cancer Death ◽

Common Cause ◽

Screening Programs ◽

Incidence And Mortality ◽

National Organizations

The incidence of colorectal cancer (CRC) is increasing worldwide and it is the second most common cause of cancer death. There is a lot of investigations and improvement to rise quality of early diagnosis, successful treatment and effective preventions of colorectal cancer. Nowadays available few guidelines of international and national organizations what support effectiveness of screening programs. Colorectal cancer screening is effective way to decrease incidence and mortality with strong evidence confirmed by a lot of investigations of different scientific groups. Currently, Ukraine doesn’t have an established colorectal cancer program, what need to be changed as soon as possible. A lot of patients in Ukraine wait at home till the beginning of clinical symptoms, what often is the representation of later stage of diseases; and of course treatment of patients with later stage of diseases need more costs for treatment and show worst results of morbidity and mortality rate compare with patients treated at the early stage of diseases. We created a simulation Markov model and demonstrated that the implementation of the national screening program for colorectal cancer in Ukraine will be cost saving and will decrease the mortality from colorectal cancer significantly.

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Super-enhancer Associated Long Non-coding RNA AC005592.2 Promotes Tumor Progression by Regulating OLFM4 in Colorectal Cancer

10.21203/rs.3.rs-60449/v1 ◽

2020 ◽

Author(s):

Linping Yan ◽

Huanhuan Chen ◽

Li Tang ◽

Pan Jiang ◽

Feng Yan

Keyword(s):

Colorectal Cancer ◽

Biological Effects ◽

Differentially Expressed ◽

Rna Seq ◽

Invasion And Migration ◽

Super Enhancer ◽

Non Coding Rna ◽

Attractive Therapeutic Target ◽

And Migration ◽

Long Non Coding Rna

Abstract Background: Super-enhancer-associated long non-coding RNAs (SE-lncRNAs) have been reported to play essential roles in tumorigenesis, but the fundamental mechanism of SE-lncRNAs in colorectal cancer (CRC) remains largely unknown. Methods: A microarray was performed to identify the differentially expressed SE-lncRNAs between CRC tissues and peritumoral tissues. A novel SE-lncRNA AC005592.2 was selected from these differentially expressed SE-lncRNAs to explore its effects in the CRC development. Fluorescence quantitative real-time PCR (qRT-PCR) was used to assay the expression of AC005592.2 in CRC tissues and cell lines. Functional assays were applied to identify the biological effects of AC005592.2 in CRC cells. Furthermore, RNA-seq was employed to predict potential targets of AC005592.2. Results: AC005592.2 was significantly increased in CRC tissues and cells. And the high expression of AC005592.2 was significantly associated with TNM stage and tumor differentiation of CRC patients. Knockdown of AC005592.2 suppressed CRC cell proliferation, invasion and migration, but promoted apoptosis, while AC005592.2 overexpression exerted precisely the opposite effects on CRC cells. Besides, AC005592.2 positively regulated the expression of olfactomedin 4 (OLFM4), which was also up-regulation in CRC tissues. Conclusion: The findings suggested that AC005592.2 is a crucial promoter of CRC progression, and may serve as an attractive therapeutic target for CRC.

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NDRG1 Inhibition of Tumor Progression in Caco2 Cells

10.21203/rs.3.rs-141427/v1 ◽

2021 ◽

Author(s):

Yixiao He ◽

Yuzhu Ji ◽

Hairong Hua ◽

Yu Zhu ◽

Peng Yu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Tumor Progression ◽

Early Stage ◽

Strong Relationship ◽

S Phase ◽

Cell Counting ◽

Invasion And Migration ◽

Caco2 Cells ◽

And Migration

Abstract Background: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Invasiveness and migration are the main cause of death, and so there is a need to find a sensitive, reliable molecular marker that can predict the migration of colorectal cancer at an early stage. NDRG1 (N-myc Downstream Regulated Gene 1) has been reported to be a multifunctional gene that has a strong relationship with tumor invasion and migration, but theories about the current role of NDRG1 in colorectal cancer remains to be conclusively determined. Methods and Results: Through lentivirus infection and CRISPR/Cas9 methods, respectively, we established that NDRG1 stably overexpressed and knocked out Caco2 cell lines. CCK8(Cell Counting kit 8) data showed that NDRG1 inhibited Caco2 proliferation. Flow cytometry further confirmed that the cell cycle can be arrested at the G1/S phase when NDRG1 overexpresses, while the number of G2 phase cells significantly increased after NDRG1 was knocked out. This means that NDRG1 inhibited the proliferation of Caco2 cells by arresting the cell cycle in the G1/S phase. Our data also demonstrated that NDRG1 promotes early cell apoptosis. The strength of invasion and migration was decreased when NDRG1 overexpressed. Conclusions: Our results underline that NDRG1 inhibits tumor progression in Caco2 cells. These findings may provide a new potential therapeutic strategy for the treatment of CRC.

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Circ_0000190 favors gastric cancer patients potentially via inhibiting miR-1252/PAK3 pathway

10.21203/rs.3.rs-29489/v1 ◽

2020 ◽

Author(s):

Gui Jun Wang ◽

Tian Yu Yu ◽

Yan Rong Li ◽

Yang Jun Liu ◽

Bei-Bei Deng

Keyword(s):

Gastric Cancer ◽

Cell Viability ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Luciferase Reporter ◽

Circular Rnas ◽

Cancer Tissue ◽

Human Gastric Cancer ◽

Rt Pcr ◽

And Migration

Abstract Background Gastric cancer accounts for 8.3% of all cancer death and is demonstrated associated with aberrant circular RNAs (circRNAs) expressions.Circ_0000190 has been noted with prognostic role in gastric cancer. We aim to investigate the role and the underlying mechanism of circ_0000190 in gastric cancer.Methods Circ_0000190 expressions were examined in gastric cancer and adjacent normal tissues by RT-PCR. With gastric cancer cell lines, circ_0000190 expression was detected by FISH and RT-PCR. After forced expression, the role of the circRNA in gastric cancer cell viability, apoptosis, proliferation, cell cycle and migration was observed. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. The association of the effectors with circ_0000190’s effects above mentioned were examined. Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190.Results Circ_0000190 was down-regulated in gastric cancer tissue and cells, with a major location in cytoplasm. After transfection, circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cycle, which was correlated with increased capase-3 and p27 expression, and decreased cyclinD expression. The circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects by circ_0000190 on the cellular processes above mentioned were blocked by miR-1252 mimics, and this was rescued after further overexpression of PAK3.Conclusions Our results revealed that circ_0000190 protected against gastric cancer, and this was via directly targeting miR-767-5p/PAK3 axis. Therefore, employing circ_0000190 might be a promising therapeutic strategy for treatment of gastric cancer.

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Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

Current Oncology ◽

10.3390/curroncol28060411 ◽

2021 ◽

Vol 28 (6) ◽

pp. 4874-4893

Author(s):

Hélder Almeida-Lousada ◽

André Mestre ◽

Sara Ramalhete ◽

Aryeh J. Price ◽

Ramon Andrade de Mello ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Stage ◽

Screening Tests ◽

Fecal Occult Blood ◽

Screening Methods ◽

Average Risk ◽

Epigenetic Biomarkers ◽

Pubmed Database ◽

Incidence And Mortality ◽

The World

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well

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Deregulation of SET is Associated with Tumor Progression and Predicts Adverse Outcome in Patients with Early-Stage Colorectal Cancer

Journal of Clinical Medicine ◽

10.3390/jcm8030346 ◽

2019 ◽

Vol 8 (3) ◽

pp. 346 ◽

Cited By ~ 10

Author(s):

Ion Cristóbal ◽

Blanca Torrejón ◽

Jaime Rubio ◽

Andrea Santos ◽

Manuel Pedregal ◽

...

Keyword(s):

Colorectal Cancer ◽

Epithelial To Mesenchymal Transition ◽

Early Stage ◽

Biological Effects ◽

Eastern Cooperative Oncology Group ◽

Soft Agar ◽

Molecular Target ◽

Clinical Impact ◽

Mesenchymal Transition ◽

Potential Clinical Impact

SET nuclear proto-oncogene (SET) deregulation is a novel molecular target in metastatic colorectal cancer (CRC). However, its role in CRC progression and its potential clinical impact in early-stage CRC patients remain unknown. Here, we studied the biological effects of SET on migration using wound-healing and transwell assays, and anchorage-independent cell growth using soft agar colony formation assays after ectopic SET modulation. SET was analyzed by immuno-staining in 231 early-stage CRC patients, and miR-199b expression was quantified by real-time PCR in a set of CRC patients. Interestingly, SET enhances cell migration, markedly affects the colony-forming ability, promotes epithelial to mesenchymal transition, and induces the expression of the MYC proto-oncogene (c-MYC) in CRC cells. SET overexpression was detected in 15.4% of cases and was associated with worse Eastern Cooperative Oncology Group (ECOG) status (p = 0.021) and relapse in stage-II CRC patients (p = 0.008). Moreover, SET overexpression predicted shorter overall survival (p < 0.001) and time to metastasis (p < 0.001), and its prognostic value was particularly evident in elderly patients. MiR-199b downregulation was identified as a molecular mechanism to deregulate SET in patients with localized disease. In conclusion, SET overexpression is a common alteration in early-stage CRC, playing an oncogenic role associated with progression and aggressiveness, and portends a poor outcome. Thus, SET emerges as a novel potential molecular target with clinical impact in early-stage in CRC.

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Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Biomolecules ◽

10.3390/biom10040632 ◽

2020 ◽

Vol 10 (4) ◽

pp. 632

Author(s):

Adam R. Markowski ◽

Agnieszka U. Błachnio-Zabielska ◽

Katarzyna Guzińska-Ustymowicz ◽

Agnieszka Markowska ◽

Karolina Pogodzińska ◽

...

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

De Novo ◽

Early Stage ◽

Early Colorectal Cancer ◽

Cancer Tissue ◽

Colorectal Cancer Tissue ◽

Ceramide Synthesis ◽

Advanced Stages ◽

Colorectal Cancer Patients

Much attention is paid to different sphingolipid pathways because of their possible use in diagnostics and treatment. However, the activity status and significance of ceramide pathways in colorectal cancer are still unclear. We analyzed colorectal cancer patients to evaluate sphingolipid profiles in the blood, colorectal cancer (CRC) tissues, and healthy surrounding colorectal tissues of the same patient, simultaneously, using liquid chromatography coupled with triple quadrupole mass spectrometry. Furthermore, we measured protein expression of de novo ceramide synthesis enzymes and mitochondrial markers in tissues using western blot. We confirmed the different sphingolipid contents in colorectal cancer tissue compared to healthy surrounding tissues. Furthermore, we showed changed amounts of several ceramides in more advanced colorectal cancer tissue and found a prominently higher circulating level of several of them. Moreover, we observed a relationship between the amounts of some ceramide species in colorectal cancer tissue and plasma depending on the stage of colorectal cancer according to TNM (tumors, nodes, metastasis) classification. We think that the combined measurement of several ceramide concentrations in plasma can help distinguish early-stage lesions from advanced colorectal cancer and can help produce a screening test to detect early colorectal cancer.

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