Colorectal cancer (CRC) is the third most common malignancy and ranks as the second leading cause of cancer-related deaths worldwide. Despite the improvements in CRC diagnosis and treatment ...approaches, a considerable proportion of CRC patients still suffers from poor prognosis due to late disease detections and lack of personalized disease managements. Recent evidences have not only provided important molecular insights into their mechanistic behaviors but also indicated that identification of cancer-specific long non-coding RNAs (LncRNAs) could benefit earlier disease detections and improve treatment outcomes in patients suffering from CRC. LncRNAs have raised extensive attentions as they participate in various hallmarks of CRC. The mechanistic evidence gleaned in the recent decade clearly reveals that lncRNAs exert their oncogenic roles by regulating autophagy, epigenetic modifications, enhancing stem phenotype and modifying tumor microenvironment. In view of their pleiotropic functional roles in malignant progression, and their frequently dysregulated expression in CRC patients, they have great potential to be reliable diagnostic and prognostic biomarkers, as well as therapeutic targets for CRC. In the present review, we will focus on the oncogenic roles of lncRNAs and related mechanisms in CRC as well as discuss their clinical potential in the early diagnosis, prognostic prediction and therapeutic translation in patients with this malignancy.
•LncRNAs extensively participate in various hallmarks of CRC.•LncRNAs affect the efficacy of chemotherapy and radiotherapy in CRC.•Detecting circulating LncRNAs benefits the early diagnosis of CRC.•Tumor-derived LncRNAs act as a reliable prognostic biomarkers.•LncRNAs can be utilized as primary targets for anti-CRC drug development.
The incidence of early-onset colorectal cancer (EO-CRC) is steadily increasing. Here, we aimed to characterise the interactions between gut microbiome, metabolites and microbial enzymes in EO-CRC ...patients and evaluate their potential as non-invasive biomarkers for EO-CRC.
We performed metagenomic and metabolomic analyses, identified multiomics markers and constructed CRC classifiers for the discovery cohort with 130 late-onset CRC (LO-CRC), 114 EO-CRC subjects and age-matched healthy controls (97 LO-Control and 100 EO-Control). An independent cohort of 38 LO-CRC, 24 EO-CRC, 22 LO-Controls and 24 EO-Controls was analysed to validate the results.
Compared with controls, reduced alpha-diversity was apparent in both, LO-CRC and EO-CRC subjects. Although common variations existed, integrative analyses identified distinct microbiome-metabolome associations in LO-CRC and EO-CRC.
enrichment and short-chain fatty acid depletion, including reduced microbial GABA biosynthesis and a shift in acetate/acetaldehyde metabolism towards acetyl-CoA production characterises LO-CRC. In comparison, multiomics signatures of EO-CRC tended to be associated with enriched
and increased tryptophan, bile acid and choline metabolism. Notably, elevated red meat intake-related species, choline metabolites and KEGG orthology (KO) pldB and cbh gene axis may be potential tumour stimulators in EO-CRC. The predictive model based on metagenomic, metabolomic and KO gene markers achieved a powerful classification performance for distinguishing EO-CRC from controls.
Our large-sample multiomics data suggest that altered microbiome-metabolome interplay helps explain the pathogenesis of EO-CRC and LO-CRC. The potential of microbiome-derived biomarkers as promising non-invasive tools could be used for the accurate detection and distinction of individuals with EO-CRC.
Epidemiological studies have investigated the association between HER2 codon 655 polymorphism and breast cancer susceptibility. However, the results are still inconclusive. To obtain a more precise ...estimation of the relationship, this meta-analysis was performed. A total of 22 studies including 9,209 cases and 10,132 controls were collected. The strength of association between HER2 codon 655 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 22 studies were pooled into the meta-analysis, there was no evidence for significant association between HER2 codon 655 polymorphism and breast cancer susceptibility (for Val/Ile vs. Ile/Ile: OR = 1.069, 95% CI = 0.976-1.172; for Val/Val vs. Ile/Ile: OR = 1.191, 95% CI = 0.922-1.538; for dominant model: OR = 1.093, 95% CI = 0.991-1.206; for recessive model: OR = 1.141, 95% CI = 0.902-1.444). In the subgroup analysis by the source of controls and ethnicity, no significant increased risk was found in all genetic models. However, the current results indicated the modest association between the HER2 Ile655Val polymorphism and Asian population (Val/Ile vs. Ile/Ile: OR = 1.207, CI = 1.006-1.450). In summary, the meta-analysis suggests that HER2 codon 655 polymorphism is not associated with the increased breast cancer risk.
As the importance of the gastrointestinal microbiome in human health and disease has been revealed via association studies, genetic manipulation tools for gut bacteria are much needed to define ...mechanisms and show causality.Exogenous DNA delivery and DNA manipulation using traditional strategies and novel clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based approaches have shown tractability in both model bacteria and non-model (‘wild’) bacteria.The development of genetic manipulation tools in gut bacteria is crucial to overcome barriers to ‘taming’ the microbiome, which allows us not only to understand host–microbiome interactions but also to accelerate microbiome engineering for novel therapeutics.
Studies of the gut microbiota have revealed associations between specific bacterial species or community compositions with health and disease, yet the causal mechanisms underlying microbiota gene–host interactions remain poorly understood. This is partly due to limited genetic manipulation (GM) tools for gut bacteria. Here, we review current advances and challenges in the development of GM approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-Cas and transposase-based systems in either model or non-model gut bacteria. By overcoming barriers to ‘taming’ the gut microbiome, GM tools allow molecular understanding of host–microbiome associations and accelerate microbiome engineering for clinical treatment of cancer and metabolic disorders. Finally, we provide perspectives on the future development of GM for gut microbiome species, where more effort should be placed on assembling a generalized GM pipeline to accelerate the application of groundbreaking GM tools in non-model gut bacteria towards both basic understanding and clinical translation.
Colorectal cancer (CRC) is one of the most prevalent cancers and one of the leading causes of cancer death. Recent studies have provided evidence that N6-methyladenosine (m6A), the most abundant RNA ...modifications in eukaryote, performs many functions in RNA metabolism including translation, splicing, storage, trafficking and degradation. Aberrant regulation of m6A modification in mRNAs and noncoding RNAs found in CRC tissues is crucial for cancer formation, progression, invasion and metastasis. Further, m6A regulators and m6A-related RNAs may become promising biomarkers, prognosis predictors as well as therapeutic targets. Here, we review the biological and clinical roles of m6A modification in CRC, and discuss the potential of m6A in clinical translation.
Recent empirical work in public finance uses the housing price response to public investment to assess the efficiency of local durable public good provision. This article explores the theoretical ...justification for this technique. It points out that the logic justifying the technique for evaluating nondurable public good provision does not translate to the durable case. A model in which investment is determined by the interaction between a budget-maximizing bureaucrat and a community's residents is used to demonstrate that the technique can falsely predict underprovision, falsely predict overprovision, or perform without error.
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