MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Stage-specific treatment of colorectal cancer: A microRNA-nanocomposite approach

Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of microRNAs(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.

Role of microRNAs in translation regulation and cancer

MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.

MicroRNAs,stem cells and cancer stem cells

This review discusses the various regulatory charac-teristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics.

MicroRNAs in neuroblastoma tumorigenesis,therapy resistance,and disease evolution

Neuroblastoma(NB)deriving from neural crest cells is the most common extra-cranial solid cancer at infancy.NB originates within the peripheral sympathetic ganglia in adrenal medulla and along the midline of the body.Clinically,NB exhibits significant heterogeneity stretching from spontaneous regression to rapid progression to therapy resistance.MicroRNAs(miRNAs,miRs)are small(19-22 nt in length)non-coding RNAs that regulate human gene expression at the post-transcriptional level and are known to regulate cellular signaling,growth,differentiation,death,stemness,and maintenance.Consequently,the function of miRs in tumorigenesis,progression and resistance is of utmost importance for the understanding of dysfunctional cellular pathways that lead to disease evolution,therapy resistance,and poor clinical outcomes.Over the last two decades,much attention has been devoted to understanding the functional roles of miRs in NB biology.This review focuses on highlighting the important implications of miRs within the context of NB disease progression,particularly miRs’influences on NB disease evolution and therapy resistance.In this review,we discuss the functions of both the“oncomiRs”and“tumor suppressor miRs”in NB progression/therapy resistance.These are the critical components to be considered during the development of novel miR-based therapeutic strategies to counter therapy resistance.

MicroRNAs in treatment-induced neuroendocrine differentiation in prostate cancer

Prostate cancer is a condition commonly associated with men worldwide.Androgen deprivation therapy remains one of the targeted therapies.However,after some years,there is biochemical recurrence and metastatic progression into castration-resistant prostate cancer(CRPC).CRPC cases are treated with second-line androgen deprivation therapy,after which,these CRPCs transdifferentiate to form neuroendocrine prostate cancer(NEPC),a highly aggressive variant of CRPC.NEPC arises via a reversible transdifferentiation process,known as neuroendocrine differentiation(NED),which is associated with altered expression of lineage markers such as decreased expression of androgen receptor and increased expression of neuroendocrine lineage markers including enolase 2,chromogranin A and synaptophysin.The etiological factors and molecular basis for NED are poorly understood,contributing to a lack of adequate molecular biomarkers for its diagnosis and therapy.Therefore,there is a need to fully understand the underlying molecular basis for this cancer.Recent studies have shown that microRNAs(miRNAs)play a key epigenetic role in driving therapy-induced NED in prostate cancer.In this review,we briefly describe the role of miRNAs in prostate cancer and CRPCs,discuss some key players in NEPCs and elaborate on miRNA dysregulation as a key epigenetic process that accompanies therapy-induced NED in metastatic CRPC.This understanding will contribute to better clinical management of the disease.