Cancer initiation and progression are governed by a complex multistep process in which successive alterations accumulate in multiple protein-coding and noncoding genes. MicroRNAs are an evolutionarily conserved class of endogenous 19- to 24-nucleotide noncoding RNAs that have been validated as key players in the balance of most cellular processes, including drug resistance. MicroRNAs change the output of protein-coding genes through posttranscriptional regulation by binding in a sequence-specific manner to the transcripts of their target genes. Resistance to therapy remains a major challenge in cancer treatment; clear solutions to this problem have yet to be found, in spite of intensive research in recent years. In this review, we explore the concept of cancer multitherapy using noncoding RNAs. We also address basic scientific questions that are related to personalized cancer treatment.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Current treatment options for inoperable HCCs have decreased therapeutic efficacy and are associated with systemic toxicity and chemoresistance. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide–dependent enzyme that is frequently overexpressed in HCC, where it promotes tumorigenicity, metastasis, and chemoresistance. SIRT1 also maintains the tumorigenic and self-renewal proprieties of liver cancer stem cells. Multiple tumor-suppressive microRNAs (miRNAs) are downregulated in HCC and, as a consequence, permit SIRT1-induced tumorigenicity. However, either directly targeting SIRT1, combining conventional chemotherapy with SIRT1 inhibitors, or upregulating tumor-suppressive miRNAs may improve therapeutic efficacy and patient outcomes. Here, we present the interaction between SIRT1, miRNAs, and liver cancer stem cells and discuss the consequences of their interplay for the development and treatment of HCC.

In a continuous and mutual exchange of information, cancer cells are invariably exposed to microenvironment transformation. This continuous alteration of the genetic, molecular and cellular peritumoral stroma background has become as critical as the management of primary tumor progression events in cancer cells. The communication between stroma and tumor cells within the extracellular matrix is one of the triggers in colon and liver carcinogenesis. All non- codingRNAs including long non-coding RNAs, microRNAs and ultraconserved genes play a critical role in almost all cancers and are responsible for the modulation of the tumor microenvironment in several malignant processes such as initiation, progression and dissemination. This review details the involvement of non codingRNAs in the evolution of human colorectal carcinoma and hepatocellular carcinoma in relationship with the microenvironment. Recent research has shown that a considerable number of dysregulated non- codingRNAs could be valuable diagnostic and prognostic biomarkers in cancer. Therefore, more in-depth knowledge of the role non- codingRNAs play in stroma-tumor communication and of the complex regulatory mechanisms between ultraconserved genes and microRNAs supports the validation of future effective therapeutic targets in patients suffering from hepatocellular and colorectal carcinoma, two distinctive entities which share quite a lot common non-coding RNAs.

Human aging is characterized by chronic low-grade inflammation known as “inflammaging.” Persistent low-level inflammation also plays a key role in all stages of breast cancer since “inflammaging” is the potential link between cancer and aging through NF-kB pathways highly influenced by specific miRs. Micro-RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at a posttranscriptional level. Inflamma-miRs have been implicated in the regulation of immune and inflammatory responses. Their abnormal expression contributes to the chronic pro-inflammatory status documented in normal aging and major age-related diseases (ARDs), inflammaging being a significant mortality risk factor in both cases. Nevertheless, the correct diagnosis of inflammaging is difficult to make and its hidden contribution to negative health outcomes remains unknown. This methodological work flow was aimed at defining crucial unanswered questions about inflammaging that can be used to clarify aging-related miRNAs in serum and cell lines as well as their targets, thus confirming their role in aging and breast cancer tumorigenesis. Moreover, we aim to highlight the links between the pro-inflammatory mechanism underlying the cancer and aging processes and the precise function of certain miRNAs in cellular senescence (CS). In addition, miRNAs and cancer genes represent the basis for new therapeutic findings indicating that both cancer and ARDs genes are possible candidates involved in CS and vice versa. Our goal is to obtain a focused review that could facilitate future approaches in the investigation of the mechanisms by which miRNAs control the aging process by acting as efficient ARDs inflammatory biomarkers. An understanding of the sources and modulation of inflamma-miRs along with the identification of their specific target genes could enhance their therapeutic potential.

The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.