scholarly journals Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Targets ◽  
Clinicopathological Characteristics ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
The Third ◽  
Current Review ◽  
Important Challenge ◽  
Prediction Of Metastasis

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

scholarly journals Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis

2021 ◽  
Vol 16 (1) ◽  
pp. 523-536
Author(s):  
Minghao Li ◽  
Jianbin Zhuang ◽  
Di Kang ◽  
Yuzhuo Chen ◽  
Weiliang Song
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Spindle Pole ◽  
Circular Rnas ◽  
Cell Progression ◽  
Crc Management ◽  
Common Malignancy

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

scholarly journals Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Xuexiu Zhang ◽  
Jianning Yao ◽  
Haoling Shi ◽  
Bing Gao ◽  
Haining Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Sp1 Transcription Factor ◽  
Reporter Assays ◽  
Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

scholarly journals MicroRNAs and Apoptosis in Colorectal Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 5353 ◽  
Author(s):  
Hsiuying Wang
Keyword(s):  
Colorectal Cancer ◽  
Treatment Resistance ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Apoptosis Induction ◽  
The Third ◽  
Anti Cancer ◽  
The World

Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is rising in developing countries. Treatment with 5-Fluorouracil (5-FU) is known to improve survival in CRC patients. Most anti-cancer therapies trigger apoptosis induction to eliminate malignant cells. However, de-regulated apoptotic signaling allows cancer cells to escape this signaling, leading to therapeutic resistance. Treatment resistance is a major challenge in the development of effective therapies. The microRNAs (miRNAs) play important roles in CRC treatment resistance and CRC progression and apoptosis. This review discusses the role of miRNAs in contributing to the promotion or inhibition of apoptosis in CRC and the role of miRNAs in modulating treatment resistance in CRC cells.

scholarly journals BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Jiang ◽  
Yue Kang ◽  
Tomasz Sewastianik ◽  
Jiao Wang ◽  
Helen Tanton ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Calcium Transients ◽  
Molecular Heterogeneity ◽  
Independent Function ◽  
The Third ◽  
Tumor Pathogenesis

AbstractColorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.

scholarly journals Aflibercept in the Treatment of Metastatic Colorectal Cancer

2012 ◽  
Vol 6 ◽  
pp. CMO.S7432 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Albert Craig Lockhart
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
The Third ◽  
Common Cancer ◽  
The Us

Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept.

scholarly journals The Emerging Role of Non-Coding RNAs in Pituitary Gland Tumors and Meningioma

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5987
Author(s):  
Soudeh Ghafouri-Fard ◽  
Atefe Abak ◽  
Bashdar Mahmud Hussen ◽  
Mohammad Taheri ◽  
Guive Sharifi
Keyword(s):  
Brain Tumors ◽  
Pituitary Gland ◽  
Pituitary Tumors ◽  
Circular Rnas ◽  
Current Review ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) are non-coding transcripts which are involved in the pathogenesis of pituitary gland tumors. LncRNAs that participate in the pathogenesis of pituitary gland tumors mainly serve as sponges for miRNAs. CLRN1-AS1/miR-217, XIST/miR-424-5p, H19/miR-93a, LINC00473/miR-502-3p, SNHG7/miR-449a, MEG8/miR-454-3p, MEG3/miR-23b-3p, MEG3/miR-376B-3P, SNHG6/miR-944, PCAT6/miR-139-3p, lncRNA-m433s1/miR-433, TUG1/miR-187-3p, SNHG1/miR-187-3p, SNHG1/miR-302, SNHG1/miR-372, SNHG1/miR-373, and SNHG1/miR-520 are identified lncRNA/miRNA pairs that are involved in this process. Hsa_circ_0001368 and circOMA1 are two examples of circRNAs that contribute to the pathogenesis of pituitary gland tumors. Meanwhile, SNHG1, LINC00702, LINC00460, and MEG3 have been found to partake in the pathogenesis of meningioma. In the current review, we describe the role of non-coding RNAs in two types of brain tumors, i.e., pituitary tumors and meningioma.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals Growth Factor Independent 1 is a tumor suppressor gene in colorectal cancer

2018 ◽  
Author(s):  
Min-Shan Chen ◽  
Yuan-Hung Lo ◽  
Xi Chen ◽  
Christopher Williams ◽  
Jessica Donnelly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
The United States ◽  
Suppressor Gene ◽  
Colorectal Adenomas ◽  
Colorectal Tumorigenesis ◽  
The Third

AbstractColorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States, causing about 50,000 deaths each year. Growth Factor-Independent 1 (GFI1) is a critical zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer and prostate cancer. However, the role of GFI1 in CRC progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced stages of non-mucinous CRC. Subcutaneous tumor models demonstrated that the re-expression of GFI1 in 4 different human CRC cell lines inhibits tumor growth by 25-60%. To further investigate the role of Gfi1 in de novo colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the distal intestine driven by the CDX2cre (Gfi1F/F; CDX2cre/+) and crossed them with ApcMin/+ mice (ApcMin/+; Gfi1F/F; CDX2cre/+). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared to littermate controls with an APC mutation alone. Furthermore, we found that compound (ApcMin/+; Gfi1F/F; CDX2cre/+) mice develop both adenomas as well as carcinoid-like tumors expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that Gfi1 deficiency promotes colorectal tumorigenesis, and suggest that loss of Gfi1 may promote formation of carcinoid cancers of the large intestines.SignificanceThese findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.

scholarly journals Colonoscopy in colorectal cancer diagnostics - the most frequently asked questions and dilemmas

2017 ◽  
Vol 70 (11-12) ◽  
pp. 359-363 ◽  
Author(s):  
Biljana Kukic
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Primary Care Physicians ◽  
Healthy Lifestyle ◽  
Developed Countries ◽  
Cancer Diagnostics ◽  
The Third ◽  
Screening And Surveillance

Colorectal cancer is the third most frequent illness of all carcinomas with an increase in the incidence of colorectal cancer in highly developed countries. 75% of patients with colorectal cancer are older than 65 years. It is believed that 66-75% of colorectal cancer could be avoided through healthy lifestyle. 75% of colorectal cancer arise from adenomatous polyp but more than 90% of adenomas will not progress to carcinoma. Colonoscopy has become the preferred method for evaluation of lower digestive symptoms and detection and treatment of colon pathology, and is considered to be the gold standard for colorectal cancer screening and surveillance. Aim of this paper is to resolve some dilemmas and answer the most frequently asked questions from primary care physicians about colonoscopy such as indications, contraindications, the role of colonoscopy in colorectal cancer screening, how often colonoscopy should be repeated, why it is so important to prepare colon and patients for colonoscopy and what type of complications can happen.

scholarly journals Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway

2020 ◽  
Author(s):  
Mengqiong Wu ◽  
Cancan Kong ◽  
Manni Cai ◽  
Weiwei Huang ◽  
Yiming Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Over Expression ◽  
Functional Assays ◽  
Cancer Intervention

Abstract CircRNAs (circular RNAs), recently identified as a critical regulator in tumorigenesis, participate in colorectal cancer (CRC) growth. However, role of hsa_circRNA_002144 in CRC was poorly understood. Firstly, hsa_circRNA_002144 showed significantly elevation in both of CRC tissues and cell lines, and suggested closely associated with poor prognosis in patients. Secondly, data from functional assays revealed that silence of hsa_circRNA_002144 inhibited CRC progression with reduced cell viability, proliferation, migration and invasion, while enhanced cell apoptosis. In addition, in vivo CRC growth and metastasis were also suppressed by knockdown of hsa_circRNA_002144. However, CRC progression was promoted with over-expression of hsa_circRNA_002144. Thirdly, hsa_circRNA_002144 colocalized with miR-615-5p in the cytoplasm of CRC cells, and decreased miR-615-5p expression. Moreover, miR-615-5p could target LARP1 (La ribonucleoprotein 1, translational regulator). Lastly, the suppressive effects of hsa_circRNA_002144 knockdown on CRC progression was reversed by LARP1 over-expression. In conclusion, hsa_circRNA_002144 could sponge miR-615-5p to promote CRC progression through regulation of LARP1, providing a therapeutic target for cancer intervention.

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