• 5-FU
• Drug resistance
• apoptosis
• cancer treatment.
• chemosensitivity
• miRNAs

• Humans
• Fluorouracil/pharmacology
• MicroRNAs/metabolism
• MicroRNAs/genetics
• Drug Resistance, Neoplasm/drug effects
• Neoplasms/drug therapy
• Neoplasms/pathology
• Neoplasms/metabolism
• Neoplasms/genetics
• Antimetabolites, Antineoplastic/pharmacology
• Thymidylate Synthase/metabolism
• Thymidylate Synthase/genetics
• Thymidylate Synthase/antagonists & inhibitors

• Biomarkers
• Gastrointestinal cancer
• NcRNAs
• Radiotherapy resistance
• Therapeutic targets

• Humans
• Neoplasm Recurrence, Local
• RNA, Untranslated/genetics
• Gastrointestinal Neoplasms/genetics
• Gastrointestinal Neoplasms/radiotherapy
• Biomarkers

• Apoptosis
• Colorectal Cancer
• Doped carbon dots
• ROS
• Saffron

• Humans
• Spectroscopy, Fourier Transform Infrared
• Crocus
• Copper/pharmacology
• Reactive Oxygen Species
• Carbon/pharmacology
• Carbon/chemistry
• Nitrogen
• Fluorescent Dyes/chemistry
• Colorectal Neoplasms/drug therapy
• Lipids
• MicroRNAs/genetics

• Lacticaseibacillus casei
• Lactobacillus casei
• HT-29
• apoptosis
• colorectal neoplasms
• miR-21

• 97002162 Aja University of Medical Sciences

• 5-fu resistance
• 5-fu analogues
• dpd inhibitors
• dpd downregulators
• formulation development

• Indian Council of Medical Research

• Cancer
• Drug resistance
• MicroRNA
• miR-21
• miR-21 inhibition

Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.

The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs).

To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein.

Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA.

The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

• 5-FU resistance
• Capecitabine
• Chemoresistance
• Colorectal cancer
• Hippo-YAP
• Micro RNA
• Wnt beta-catenin
• ceRNA network
• miRNAs

• 5-FU
• Colorectal Cancer
• MicroRNA-21
• Synergy Effect
• Tangeretin

• Colorectal cancer (CRC)
• Oncogenic miRNAs
• Tumor suppressor (TS) miRNAs

Drug resistance in tumors is a major issue, limiting the curative efficacy of currently available cancer chemotherapeutics. 5-Fluorouracil (5-FU) is a commonly applied therapeutic drug in colon cancer patient regimens; however, the majority of patients develop resistance to 5-FU in the later stages of the disease, rendering this chemotherapy ineffective. Drug resistance is the main factor underlying the poor prognosis of patients with colon cancer. In recent years, a number of studies have confirmed that long non-coding (lnc)RNAs may play vital roles in tumor resistance. In the present study, the Gene Expression Omnibus (GEO) and lncRNADisease2 databases were screened for colon cancer-associated expression patterns of lncRNA plasmacytoma variant translocation 1 (PVT1). Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in PVT1 expression in resistant cell lines, and a Cell Counting Kit-8 (CCK-8) assay kit was used to assess the effects of PVT1 knockdown on the half maximal inhibitory concentrations of parental and 5-FU-resistant HCT116 cells. Subsequently, CCK-8, clone formation, and flow cytometric assays were performed to investigate the effects of PVT1 knockdown on the sensitivity of HCT116-5FU-resistant cells to 5-FU. Dual-luciferase assay, RNA pull-down and RNA immunoprecipitation assays verified the interactive regulation of PVT1, miR-486-5p and cyclin dependent kinase 4 (CDK4). PVT1 was highly expressed in HCT116-5FU-resistant cells, as compared to its expression in HCT116 parental cells. PVT1 knockdown significantly reduced the resistance of HCT116-5FU-resistant cells to 5-FU. In addition, PVT1 upregulated CDK4 expression by adsorbing miR-486-5p; however, CDK4 overexpression restored the effects of miR-486-5p inhibition on HCT116-5-FU-resistant cells. Additionally, PVT1 knockdown partially rescued CDK4 overexpression in HCT116-5-FU-resistant cells. On the whole, the findings of the present study suggest that PVT1 promotes the resistance of colon cancer cells to 5-FU by regulating the miR-486-5p/CDK4 axis. Therefore, PVT1 may prove to be a potential target for counteracting resistance to 5-FU in colon cancer therapy.

Colorectal cancer (CRC) is one of most common cancers worldwide, with high rates of mortality. Epidemiological findings demonstrate that coffee consumption reduces the risk of developing CRC by ~13%. In general, in vivo and in vitro findings demonstrate the antiproliferative, antioxidant and proapoptotic effects of brewed coffee or major bioavailable coffee compounds. Thus, it was assessed whether caffeine (CAF) and/or chlorogenic acid (CGA) attenuates the early-stage of chemically induced mouse colon carcinogenesis. Male Swiss mice were submitted to a 1,2-dimethylhydrazine/deoxycholic acid (DMH/DCA)-induced colon carcinogenesis model. These animals received CAF (50 mg/kg), CGA (25 mg/kg) or CAF+CGA (50 + 25 mg/kg) intragastrically for five times/week for ten weeks. CAF+CGA had the most pronounced effects on decreasing epithelial cell proliferation (Ki-67) and increasing apoptosis (cleaved caspase-3) in colonic crypts. This treatment also decreased the levels of proinflammatory cytokines IL-6, IL-17 and TNF-α, and downregulated the oncomiR miR-21a-5p in the colon. Accordingly, the analysis of miR-21a-5p targets demonstrated the genes involved in the negative regulation of proliferation and inflammation, and the positive regulation of apoptosis. Ultimately, CAF+CGA attenuated preneoplastic aberrant crypt foci (ACF) development. Our findings suggest that a combination of coffee compounds reduces early-stage colon carcinogenesis by the modulation of miR-21a-5p expression, highlighting the importance of coffee intake to prevent CRC.

• 1,2-Dimethylhydrazine
• Animals
• Caffeine/pharmacology
• Carcinogenesis
• Chlorogenic Acid/pharmacology
• Chlorogenic Acid/therapeutic use
• Coffee
• Colon/metabolism
• Colonic Neoplasms/chemically induced
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/genetics
• Male
• Mice
• MicroRNAs/genetics
• MicroRNAs/pharmacology

• 5-fluorouracil
• Colorectal cancer
• Drug resistance
• MicroRNA

• Cell Line, Tumor
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Drug Resistance, Neoplasm/genetics
• Fluorouracil/pharmacology
• Fluorouracil/therapeutic use
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/metabolism
• Neoplasm Recurrence, Local/genetics

Radiotherapy (RT), or radiation therapy, has been widely used in clinical practice for the treatment of local advanced gastrointestinal carcinoma. RT causes DNA double-strand breaks leading to cell cytotoxicity and indirectly damages tumor cells by activating downstream genes. Non-coding RNA (including microRNAs, long non-coding RNAs (ncRNAs), and circular RNAs) is a type of RNA that does not encode a protein. As the field of ncRNAs increasingly expands, new complex roles have gradually emerged for ncRNAs in RT. It has been shown that ncRNAs can act as radiosensitivity regulators in gastrointestinal carcinoma by affecting DNA damage repair, cell cycle arrest, irradiation-induced apoptosis, cell autophagy, stemness, EMT, and cell pyroptosis. Here, we review the complex roles of ncRNAs in RT and gastrointestinal carcinoma. We also discuss the potential clinical significance and predictive value of ncRNAs in response to RT for guiding the individualized treatment of patients. This review can serve as a guide for the application of ncRNAs as radiosensitivity enhancers, radioresistance inducers, and predictors of response in RT of gastrointestinal carcinoma.

• Beijing Xisike Clinical Oncology Research Foundation
• Wu Jieping Medical Foundation

• gastrointestinal cancers
• non-coding RNAs
• response to chemotherapy

• ABC transporters
• Anticancer
• Drug resistance
• Vipera ammodytes

Cellular metabolism alterations have been recognized as one of the most predominant hallmarks of colorectal cancers (CRCs). It is precisely regulated by many oncogenic signaling pathways in all kinds of regulatory levels, including transcriptional, post-transcriptional, translational and post-translational levels. Among these regulatory factors, epigenetics play an essential role in the modulation of cellular metabolism. On the one hand, epigenetics can regulate cellular metabolism via directly controlling the transcription of genes encoding metabolic enzymes of transporters. On the other hand, epigenetics can regulate major transcriptional factors and signaling pathways that control the transcription of genes encoding metabolic enzymes or transporters, or affecting the translation, activation, stabilization, or translocation of metabolic enzymes or transporters. Interestingly, epigenetics can also be controlled by cellular metabolism. Metabolites not only directly influence epigenetic processes, but also affect the activity of epigenetic enzymes. Actually, both cellular metabolism pathways and epigenetic processes are controlled by enzymes. They are highly intertwined and are essential for oncogenesis and tumor development of CRCs. Therefore, they are potential therapeutic targets for the treatment of CRCs. In recent years, both epigenetic and metabolism inhibitors are studied for clinical use to treat CRCs. In this review, we depict the interplay between epigenetics and cellular metabolism in CRCs and summarize the underlying molecular mechanisms and their potential applications for clinical therapy.

• cellular metabolism
• colorectal cancer
• epigenetics
• targeted therapy
• tumorigenesis

• alternative cancer therapies
• anticancer diet
• calories restriction
• targeting cancer metabolism

• Animals
• Biomarkers
• Diet, Ketogenic
• Disease Management
• Disease Susceptibility
• Eating
• Energy Metabolism
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Humans
• Metabolic Networks and Pathways
• Neoplasms/diet therapy
• Neoplasms/epidemiology
• Neoplasms/etiology
• Neoplasms/prevention & control
• Signal Transduction
• Treatment Outcome

MiRNAs are of great interest within colorectal cancers in diagnosis, prognosis, and within the field of personalized treatments; they are present within different biological fluids such as blood and can lead to specific information for daily clinical use. Herein, we review the current literature focusing on miRNAs as potential diagnostic and prognostic biomarkers in patients treated for colorectal cancers. Detection and analysis of miRNA expression are cost-effective and lead to high sensitivity and specificity rates. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal, either diagnostic, prognostic, or theranostic, thanks to multicentric prospective studies.

MiRNAs have recently become a subject of great interest within cancers and especially colorectal cancers in diagnosis, prognosis, and therapy decisions; herein we review the current literature focusing on miRNAs in colorectal cancers, and we discuss future challenges to use this tool on a daily clinical basis. In liquid biopsies, miRNAs seem easily accessible and can give important information toward each step of the management of colorectal cancers. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal thanks to multicentric prospective studies. Conclusions: by their diversity and the feasibility of their use, miRNAs are getting part of the armamentarium of healthcare management of colorectal cancers.

• MiRNA
• biomarker
• colorectal cancer
• diagnostic
• prognosis

• cancer
• digestive system
• gastrointestinal tract
• liver
• miR-21
• pancreas

• cancer
• combination therapy
• drug resistance
• miR-21

• biomarker
• expression
• fluorouracil
• lncRNA
• miRNA

• 5-fluorouracil
• chemoresistance
• circRNAs
• cisplatin
• colorectal cancer
• doxorubicin
• lncRNAs
• miRNAs
• ncRNAs
• oxaliplatin

• cancer stem cells
• colorectal cancer
• immune checkpoint inhibitors
• immunotherapy
• microsatellite instability
• organoids
• patient-derived xenografts
• personalized chemotherapystem cell markers
• stem cell signaling pathways
• targeted therapies

• AC133 Antigen/biosynthesis
• Colorectal Neoplasms/pathology
• Hedgehog Proteins/metabolism
• Humans
• Immune Checkpoint Inhibitors/pharmacology
• Immunotherapy, Adoptive/methods
• Janus Kinases/metabolism
• MicroRNAs/metabolism
• RNA, Long Noncoding/metabolism
• Receptors, Notch/metabolism
• STAT Transcription Factors/metabolism
• Signal Transduction
• Stem Cells/metabolism
• Wnt Proteins/metabolism
• beta Catenin/metabolism

• CA204881, CA206026, CA56036 NCI NIH HHS
• R01 CA206026 NCI NIH HHS
• T32 GM008562 NIGMS NIH HHS
• R01 CA204481 NCI NIH HHS
• P30 CA056036 NCI NIH HHS
• U.S. Department of Defense
• National Cancer Institute
• National Institute of General Medical Sciences

Colorectal cancer (CRC) is the third major cause of cancer-related death worldwide, and fluorouracil (5-FU) is widely used in the treatment of CRC. However, acquired resistance to 5-FU has become an obstacle in the effective treatment of CRC. Adenosine triphosphate (ATP)-binding cassette sub-family G member 2 (ABCG2) has been found highly expressed in CRC patients with poor responsiveness to folinic acid/5-FU/irinotecan. However, the mechanisms of 5-FU resistance regulated by ABCG2 in CRC cells remain to be comprehensively understood. We aimed to explore the upstream mechanisms of ABCG2 involved in the regulation of chemoresistance in CRC cells.

We investigated the potential mechanisms of 5-FU resistance in HCT116, RKO, RKO microRNA-21 (miR-21) knockout, and acquired 5-FU-resistant HCT116 (HCT116/FUR) cells. The biochemical and biological analyses were conducted using semiquantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, transfections, and rescue experiments, along with cell proliferation, viability, and colony formation assays. In order to investigate the efficacy of inhibiting the c-Jun NH2 terminal kinase (JNK) pathway to overcome 5-FU resistance, HCT116 and 5-FU-resistant HCT116 cells were inoculated into BALB/c-nu/nu mice to establish the cell-derived xenograft model.

The results showed that ABCG2 expression in HCT116/FUR cells was higher compared to HCT116 cells. Overexpression of ABCG2 decreased sensitivity to 5-FU in HCT116 cells, but knockdown of ABCG2 decreased the survival rate in HCT116/FUR cells. Additionally, repressing programmed cell death 4 (PDCD4) activated the JNK pathway in HCT116/FUR cells. Overexpression of PDCD4 inhibited phosphorylation of c-Jun and ABCG2 expression, and recovered sensitivity to 5-FU in HCT116/FUR cells. Moreover, treatment with the JNK pathway inhibitor SP600125 downregulated ABCG2 expression and rescued sensitivity to 5-FU in HCT116/FUR cells. We also found that miR-21 expression in HCT116/FUR cells was higher compared to HCT116 cells. Finally, 5-FU treatment in combination with SP600125 significantly decreased tumorigenicity compared to other treatments in vivo.

Our results demonstrated that 5-FU treatment upregulated miR-21, which directly repressed PDCD4, and subsequently activated the JNK pathway, leading to the upregulation of ABCG2 in CRC cells. Inhibition of the JNK pathway overcame acquired 5-FU resistance both in vivo and in vitro.

• ABCG2
• Colorectal cancer (CRC)
• PDCD4
• c-Jun N-terminal kinase
• chemoresistance
• fluorouracil (5-FU)
• microRNA-21 (miR-21)

MircoRNA-21 (miR-21) was found to be highly expressed in various solid tumors, and its oncogenic properties have been extensively studied in recent years. However, the reason why miR-21 is highly expressed in various tumors remains elusive. Here, we found that the expression of miR-21 was negatively correlated with the expression of vacuole membrane protein-1 (VMP1) in colorectal cancer. Transcription of VMP1 activated either by small activating RNA (saRNA) or transcriptional activator GLI3 inhibited miR-21 expression through reducing its transcripts of VMP1-miR-21 and pri-miR-21, while no significant change in miR-21 expression after exogenous overexpression VMP1 in colorectal cancer cell HCT116. Considering the overlapping location of VMP1 and miR-21 gene in genome, the result suggested that the transcription of miR-21 was inhibited by the endogenous transcriptional activation of VMP1. Furthermore, we identified that miR-21 inhibited the activation and nuclear translocation of transcription factor EB (TFEB) through reducing the inhibitory of PTEN on AKT phosphorylation, which can directly activate the transcription of VMP1. Loss of miR-21 significantly increased VMP1 expression, which could be blocked by PTEN inhibitor (VO-Ohpic) or TFEB siRNA. These results showed that miR-21 negatively regulated VMP1 transcription through the PTEN/AKT/TFEB pathway, and TFEB-induced transcriptional activation of VMP1 could inhibit miR-21 expression, thus forming a feedback regulatory loop of miR-21/VMP1. We further found that disrupting the miR-21/VMP1 feedback loop will decrease the expression of miR-21, reduce the malignancy, and increase their sensitivity to 5-fluorouracil in colorectal cancer cells. Taken together, our results revealed a novel regulatory mechanism of miR-21 expression, and targeting the miR-21/VMP1 feedback loop may provide a new approach to inhibit miR-21 expression in colorectal cancer cells.

• biomarkers
• colorectal cancer
• diabetes mellitus
• glucose
• insulin
• microRNA

Background: Patients with locally advanced rectal adenocarcinoma (LARC) are treated with neoadjuvant chemoradiotherapy (CRT). However, biomarkers for patient selection are lacking, and the association between miRNA expression and treatment response and oncological outcomes is unclear.

Objectives: To investigate miRNAs as predictors of response to neoadjuvant CRT and its association with oncological outcomes.

Methods: This retrospective study analyzed miRNA expression (miR-16, miR-21, miR-135b, miR-145, and miR-335) in pre- and post-chemoradiation rectal adenocarcinoma tissue and non-neoplastic mucosa in 91 patients treated with neoadjuvant CRT (50.4 Gy) and proctectomy. Two groups were defined: a pathological complete responders group (tumor regression grade—TRG 0) and a pathological incomplete responders group (TRG 1, 2, and 3).

Results: miR-21 and miR-135b were upregulated in tumor tissue of incomplete responders comparing with non-neoplastic tissue (p = 0.008 and p < 0.0001, respectively). Multivariate analysis showed significant association between miR-21 in pre-CRT tumor tissue and response, with a 3.67 odds ratio (OR) of incomplete response in patients with higher miR-21 levels (p = 0.04). Although with no significance, patients treated with 5-fluorouracil (5-FU) presented reduced odds of incomplete response compared with those treated with capecitabine (OR = 0.19; 95% confidence interval (CI) 0.03–1.12, p = 0.05). Moreover, significant differences were seen in overall survival (OS) in relation to clinical TNM stage (p = 0.0004), cT (p = 0.0001), presence of distant disease (p = 0.002), mesorectal tumor deposits (p = 0.003), and tumor regression grade (p = 0.04).

Conclusion: miR-21 may predict response to CRT in rectal cancer (RC).

• biomarkers
• chemoradiotherapy response
• miR-21
• rectal cancer
• tumor regression grade

• biomarkers
• colorectal cancer
• drug resistance
• miRNAs
• targeted therapy

• 5-fluorouracil
• colorectal cancer
• resistance mechanism

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.

• apoptosis
• colorectal cancer
• microRNA
• resistance

• Apoptosis
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Drug Resistance, Neoplasm
• Fluorouracil/therapeutic use
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• Signal Transduction

• Cell-cell adhesion
• Colorectal cancer
• Multicellular tumor spheroid
• microRNA

• Immune checkpoint blockade
• Noncoding RNA
• PD-1/PD-L1 pathway
• microRNA

• Animals
• B7-H1 Antigen/immunology
• Humans
• Neoplasms/immunology
• Programmed Cell Death 1 Receptor/immunology
• RNA, Untranslated

• 81572122 National Natural Science Foundation of China

The human microbiota is made up of the fungi, bacteria, protozoa and viruses cohabiting within the human body. An altered microbiota can provoke diseases such as cancer. The mechanisms by which a modified microbiota can intervene in the onset and progression of neoplastic diseases are manifold. For instance, these include the effects on the immune system and the onset of obesity. A different mechanism seems to be constituted by the continuous and bidirectional relationships existing between microbiota and miRNAs. MiRNAs emerged as a novel group of small endogenous non-coding RNAs from that control gene expression. Several works seem to confirm the presence of a close connection between microbiota and miRNAs. Although the main literature data concern the correlations between microbiota, miRNAs and colon cancer, several researches have revealed the presence of connections with other types of tumour, including the ovarian tumour, cervical carcinoma, hepatic carcinoma, neoplastic pathologies of the central nervous system and the possible implication of the microbiota-miRNAs system on the response to the treatment of neoplastic pathologies. In this review, we summarise the physiological and pathological functions of the microbiota on cancer onset by governing miRNA production. A better knowledge of the bidirectional relationships existing between microbiota and miRNAs could provide new markers for the diagnosis, staging and monitoring of cancer and seems to be a promising approach for antagomir-guided approaches as therapeutic agents.

• biomarkers
• cancer
• colorectal cancer
• immune system
• miRNA
• microbiota
• ovarian cancer

• NADPH oxidase
• cancer
• miRNA
• oxidative stress
• reactive oxygen species

• Animals
• Humans
• MicroRNAs/genetics
• NADPH Oxidases/genetics
• NADPH Oxidases/metabolism
• Neoplasms/enzymology
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/therapy
• Reactive Oxygen Species/metabolism

• I01 BX002494 BLRD VA

• IRF2BP2
• connective tissue growth factor
• gastric cancer
• prognosis

• ABTB1
• Colorectal cancer
• PLZF
• miR-4319

• Cell Cycle/genetics
• Cell Movement/genetics
• Cell Proliferation/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• HCT116 Cells
• HEK293 Cells
• Humans
• Kaplan-Meier Estimate
• MicroRNAs/genetics
• MicroRNAs/isolation & purification
• MicroRNAs/metabolism
• Neoplasm Invasiveness/genetics
• Prognosis
• Promyelocytic Leukemia Zinc Finger Protein/metabolism
• RNA, Small Interfering/metabolism
• Real-Time Polymerase Chain Reaction
• Repressor Proteins/genetics

• National Science Foundation
• Wuxi Medical Emphasis Disciplines Funding
• Wuxi Science and Technology Development Plan
• Clinical Medicine Project of Jiangsu Province
• National Sciences Foundation of Jiangsu Province

The compound 5’-deoxy-5-fluorouridine (5’-DFUR) is a prodrug of the anti-tumor drug 5-fluorouracil (5-FU). Thymidine phosphorylase (TP) is an enzyme that can convert 5’-DFUR to its active form 5-FU and the expression of TP is upregulated in various cancer cells. In this study, 5’-DFUR associated with amphiphilic copolymer poly(ε-caprolactone)-methoxy poly(ethylene glycol) (5’-DFUR-PCL-MPEG) was synthesized, characterized, and self-assembled into functional polymeric micelles. To demonstrate that the prodrug 5’-DFUR could convert into cytotoxic 5-fluorouracil (5-FU) by endogenous TP, HT-29 colorectal cancer cells were treated with 5’-DFUR-PCL-MPEG polymeric micelles for various time periods. Chemotherapeutic drugs doxorubicin (DOX) and 7-ethyl-10-hydroxycamptothecin (SN-38) were also encapsulated separately into 5’-DFUR-PCL-MPEG polymeric micelles to create a dual drug-loaded system. HT-29 cells were treated with DOX or SN-38 encapsulated 5’-DFUR-PCL-MPEG polymeric micelles to examine the efficacy of dual drug-loaded micelles. As a result, HT-29 cells treated with 5’-DFUR-PCL-MPEG polymeric micelles showed up to 40% cell death rate after a 72-h treatment. In contrast, HT-29 cells challenged with DOX or SN-38 encapsulated 5’-DFUR-incorporated polymeric micelles showed 36% and 31% in cell viability after a 72-h treatment, respectively.

• 5-fluorouracil
• 5’-DFUR
• SN-38
• doxorubicin
• polymeric micelle
• prodrug
• thymidine phosphorylase

Colorectal cancer (CRC) is responsible for one of the major cancer incidence and mortality worldwide. It is well known that MicroRNAs (miRNAs) play vital roles in maintaining the cell development and other physiological processes, as well as, the aberrant expression of numerous miRNAs involved in CRC progression. MiRNAs are a class of small, endogenous, non-coding, single-stranded RNAs that bind to the 3’-untranslated region (3′-UTR) complementary sequences of their target mRNA, resulting in mRNA degradation or inhibition of its translation as a post-transcriptional regulators. Moreover, miRNAs also can target the long non-coding RNA (lncRNA) to regulate the expression of its target genes involved in proliferation and metastasis of CRC. The functions of these dysregulated miRNAs appear to be context specific, with evidence of having a dual role in both oncogenes and tumor suppression depending on the cellular environment in which they are expressed. Therefore, the unique expression profiles of miRNAs relate to the diagnosis, prognosis, and therapeutic outcome in CRC. In this review, we focused on several oncogenic and tumor-suppressive miRNAs specific to CRC, and assess their functions to uncover the molecular mechanisms of tumor initiation and progression in CRC. These data promised that miRNAs can be used as early detection biomarkers and potential therapeutic target in CRC patients.

• biomarkers
• colorectal cancer (CRC)
• oncogenic miRNAs
• tumor-suppressive miRNAs

• 5-FU resistance
• colorectal cancer
• microRNA

• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Drug Resistance, Neoplasm/genetics
• Fluorouracil/adverse effects
• Fluorouracil/therapeutic use
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• MicroRNAs/genetics
• Signal Transduction/drug effects

• colorectal cancer
• inflammatory markers
• microRNA
• prognosis
• survival outcomes

• Biomarkers/metabolism
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Humans
• Inflammation/genetics
• Inflammation/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Models, Biological
• Prognosis

• Comparison
• Hypomethylation
• Microsatellite and chromosomal instability
• Molecular mechanism