Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.

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Differentially Expressed miRNA-Gene Targets Related to Intramuscular Fat in Musculus Longissimus Dorsi of Charolais × Holstein F2-Crossbred Bulls

Genes ◽

10.3390/genes11060700 ◽

2020 ◽

Vol 11 (6) ◽

pp. 700

Author(s):

Bilal Ahmad Mir ◽

Henry Reyer ◽

Katrin Komolka ◽

Siriluck Ponsuksili ◽

Christa Kühn ◽

...

Keyword(s):

Target Genes ◽

Mirna Gene ◽

Target Prediction ◽

Microarray Experiment ◽

Intramuscular Fat ◽

Differentially Expressed ◽

Longissimus Dorsi ◽

P Value ◽

Mirna Expression Pattern ◽

Differentially Expressed Mirnas

Intramuscular fat (IMF) is a meat quality indicator associated with taste and juiciness. IMF deposition, influenced by genetic and non-genetic factors, occurs through a transcriptionally coordinated process of adipogenesis. MicroRNAs (miRNAs) are transcriptional regulators of vital biological processes, including lipid metabolism and adipogenesis. However, in bovines, limited data on miRNA profiling and association with divergent intramuscular fat content, regulated exclusively by genetic parameters, have been reported. Here, a microarray experiment was performed to identify and characterize the miRNA expression pattern in the Musculus longissimus dorsi of F2-cross (Charolais × German Holstein) bulls with high and low IMF. A total of 38 differentially expressed miRNAs (DE miRNAs), including 33 upregulated and 5 downregulated (corrected p-value ≤ 0.05, FC ≥ ±1.2), were reported. Among DE miRNAs, the upregulated miRNAs miR-105a/b, miR-695, miR-1193, miR-1284, miR-1287-5p, miR-3128, miR-3178, miR-3910, miR-4443, miR-4445 and miR-4745, and the downregulated miRNAs miR-877-5p, miR-4487 and miR-4706 were identified as novel fat deposition regulators. DE miRNAs were further analyzed, along with previously identified differentially expressed genes (DEGs) from the same samples and predicted target genes, using multiple bioinformatic approaches, including target prediction tools and co-expression networks, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. We identified DE miRNAs and their gene targets associated with bovine intramuscular adipogenesis, and we provide a basis for further functional investigations.

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Genome-wide profiling of miRNA expression patterns in tubal endometriosis

Reproduction ◽

10.1530/rep-18-0631 ◽

2019 ◽

Vol 157 (6) ◽

pp. 525-534 ◽

Cited By ~ 4

Author(s):

Hang Qi ◽

Guiling Liang ◽

Jin Yu ◽

Xiaofeng Wang ◽

Yan Liang ◽

...

Keyword(s):

Pathway Analysis ◽

Mirna Expression ◽

Gene Networks ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Mirna Gene ◽

Differentially Expressed ◽

Signal Pathways ◽

Differentially Expressed Mirnas

MicroRNA (miRNA) expression proﬁles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjustedPvalue <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.

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Identification of a Key Competing Endogenous RNA Axis, “COL5A1/miR-137-3p/FSTL1”, Associated With Gastric Cancer Progression by Integrated Bioinformatics Analyses and Experimental Verification

10.21203/rs.3.rs-824329/v1 ◽

2021 ◽

Author(s):

Ming Yang ◽

Zhixing Lu ◽

Liang Li ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Target Gene ◽

Target Genes ◽

Differentially Expressed ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Bioinformatics Analyses ◽

Immune Infiltration ◽

Differentially Expressed Mirnas

Abstract Background MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer (GC), but this role has not been fully clarified. Therefore, our goal was to find the key miRNA-mRNA regulatory network in GC by combining a variety of bioinformatics and experimental analyses. Methods Differentially expressed miRNAs (DEMs) and genes (DEGs) were screened from TCGA and GEO, respectively. Survival-related differentially expressed miRNAs (SRDEMs) were determined by Cox proportional hazards regression and lasso regression analyses. Differentially expressed target genes (DETGs) of SRDEMs were predicted by TargetScan and miRDB and overlapped with DEGs. We constructed a protein–protein interaction (PPI) network of DETGs and conducted weighted gene coexpression network analysis (WGCNA) to screen the hub genes. Then, qRT–PCR and western blotting were performed to detect the expression level, and a dual-luciferase reporter assay was conducted to verify the binding of miRNA and mRNAs. CCK-8, EdU, wound healing and Transwell assays were conducted to compare the proliferation, migration and invasion abilities of GC cells in the different groups. Results We identified 11 SRDEMs and 233 DETGs, from which we selected miR-137-3p and its target gene COL5A1 for further research because of their key roles in the results of the bioinformatics analyses. Then, we showed that miR-137-3p was significantly downregulated in GC and that overexpression of miR-137-3p suppressed the proliferation, invasion and migration of GC cells by targeting COL5A1. Furthermore, we found that COL5A1 could regulate the expression of FSTL1 and GC progression by sponging miR-137-3p. Finally, bioinformatics analyses showed that FSTL1 might promote GC progression by regulating the immune infiltration of GC. Conclusions miR-137-3p played a tumor-suppressive role in GC, and its target gene COL5A1 could competitively bind miR-137-3p to upregulate the expression of FSTL1, which affects immune infiltration.

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Cluster mir-17–92 is differentially expressed in colon cancer patients and embryonic colon tissue and may contribute to carcinogenesis through E2F1 expression

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10525 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10525-10525

Author(s):

J. Garcia-Foncillas ◽

A. Navarro ◽

E. Bandres ◽

R. Artells ◽

I. Moreno ◽

...

Keyword(s):

Colon Cancer ◽

Embryonic Development ◽

Mirna Expression ◽

Target Genes ◽

Tumor Tissue ◽

Stage I ◽

Differentially Expressed ◽

Embryonic Tissue ◽

Colon Tissue ◽

E2f1 Expression

10525 Background: Mature microRNAs (miRNA) are small RNA molecules that act as negative regulators of gene expression, either inhibiting mRNA by blocking its translation into protein or destroying it by RNA interference. Many miRNAs participate in essential processes, including normal embryonic development and carcinogenesis. Methods: We have assessed 156 mature miRNAs in colon tissue from eleven 7–12-week human embryos and 44 colorectal human samples. Data were analyzed using TIGR Multiexperiment viewer. Two multivariate permutation test were performed. Potential target genes of differentially expressed miRNAs are evaluated by western blot. Results: 28 miRNAs were expressed in stage I tumor tissue but not in the corresponding normal tissue, and 13 of these 28 miRNAs (46%) were also expressed in embryonic tissue. Sixty-four miRNAs were differentially expressed in stage II tumor tissue, and 29 of these 64 miRNAs (45%) were also expressed in embryonic tissue. Some miRNAs that are active during embryogenesis, such as mir-17–92, miR-181a, miR-181b and miR-181c (linked to HOXA11), and miR-10a (linked to HOXB8)23, are also expressed during tumor growth. The analysis of 156 miRNAs by K-means support revealed two well-differentiated groups: the embryos of 7–8 weeks and those of 9–12 weeks. Lower miRNA expression was also observed in tumor tissue from stage I in comparison with stage II disease (P=0.014). Analysis of potential target genes revealed that cluster mir-17–92 is differentially expressed in colon cancer and embryonic tissue and may contribute to carcinogenesis through E2F1 expression. Conclusions: Our findings indicate that miRNAs expressed during the embryonic development of the human colon are also expressed in colon tumor tissue. During colon organogenesis, miRNA expression is at first high, while cells are still undifferentiated, but expression levels decrease as cells become more differentiated. In contrast, during the development of colorectal cancer, this process is reversed. No significant financial relationships to disclose.

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Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

Current Bioinformatics ◽

10.2174/1574893615666200207092410 ◽

2021 ◽

Vol 15 (8) ◽

pp. 927-936 ◽

Cited By ~ 3

Author(s):

Yan Peng ◽

Yuewu Liu ◽

Xinbo Chen

Keyword(s):

Drought Stress ◽

Target Genes ◽

Hot Spot ◽

Interaction Network ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Promising Tool ◽

Differentially Expressed Mirnas ◽

Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identiﬁed. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

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Role of MicroRNAs in Colon Cancer Progression and Metastasis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200825184924 ◽

2020 ◽

Vol 20 ◽

Author(s):

Shruthi Sanjitha Sampath ◽

Sivaramakrishnan Venkatabalsubramanian ◽

Satish Ramalingam

Keyword(s):

Colon Cancer ◽

Cancer Progression ◽

Target Genes ◽

Tumour Progression ◽

Intestinal Barrier ◽

Colon Cancer Progression ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

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Lack of Inferior Mesenteric Artery in a Sigmoid Colon Cancer

Nippon Daicho Komonbyo Gakkai Zasshi ◽

10.3862/jcoloproctology.71.37 ◽

2018 ◽

Vol 71 (1) ◽

pp. 37-40

Author(s):

Sunao Ito ◽

Nobuhiro Haruki ◽

Hideki Tsuji ◽

Koshiro Harata

Keyword(s):

Colon Cancer ◽

Sigmoid Colon ◽

Mesenteric Artery ◽

Inferior Mesenteric Artery ◽

Sigmoid Colon Cancer

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Laparoscopic-assisted colectomy and lymphadenectomy without peritoneal insufflation for sigmoid colon cancer patients

Diseases of the Colon & Rectum ◽

10.1007/bf02148859 ◽

1995 ◽

Vol 38 (5) ◽

pp. 550-552 ◽

Cited By ~ 8

Author(s):

Yutaka J. Kawamura ◽

Hideaki Saito ◽

Toshio Sawada ◽

Tetsuichiro Muto ◽

Hideo Nagai

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Sigmoid Colon ◽

Sigmoid Colon Cancer ◽

Laparoscopic Assisted

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Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

Case Reports in Gastroenterology ◽

10.1159/000445976 ◽

2016 ◽

Vol 10 (1) ◽

pp. 204-211 ◽

Cited By ~ 2

Author(s):

Nobuhiro Morinaga ◽

Naritaka Tanaka ◽

Yoshinori Shitara ◽

Masatoshi Ishizaki ◽

Takatomo Yoshida ◽

...

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Brain Metastasis ◽

Brain Metastases ◽

Sigmoid Colon ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Sigmoid Colon Cancer ◽

Ovarian Lesion ◽

Node Metastases

Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT)/calcium folinate (leucovorin, LV) was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX) were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

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