DNA damage response signaling pathways as important targets for combination therapy and chemotherapy sensitization in osteosarcoma.

Osteosarcoma (OS) is the most common bone malignancy that occurs most often in young adults, and adolescents with a survival rate of 20% in its advanced stages. Nowadays, increasing the effectiveness of common treatments used in OS has become one of the main problems for clinicians due to cancer cells becoming resistant to chemotherapy. One of the most important mechanisms of resistance to chemotherapy is through increasing the ability of DNA repair because most chemotherapy drugs damage the DNA of cancer cells. DNA damage response (DDR) is a signal transduction pathway involved in preserving the genome stability upon exposure to endogenous and exogenous DNA-damaging factors such as chemotherapy agents. There is evidence that the suppression of DDR may reduce chemoresistance and increase the effectiveness of chemotherapy in OS. In this review, we aim to summarize these studies to better understand the role of DDR in OS chemoresistance in pursuit of overcoming the obstacles to the success of chemotherapy.

Role of exosomal miRNA in chemotherapy resistance of Colorectal cancer: A systematic review.

The third most common malignancy has been identified as Colorectal cancer (CRC) that conducive to death in most cases. Chemoresistance is a common obstacle to CRC treatment. Circulating exosomal microRNAs (miRNAs) have been shown to reverse chemo-resistance and are promising biomarkers for CRC. The capacity of engineered exosomes to cross biological barriers and deliver functional miRNAs could be used to achieve these proposes. The object of this review is the investigation of the role of exosomal miRNA in the chemo-resistance, diagnosis, and prognosis of CRC. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic databases, PubMed, EMBASE, Web of Science, Scopus were searched from January 1990 to November 2020. Ultimately, eight articles included five in vitro (16 cell lines) and three in vivo examinations. Three studies demonstrated that increasing or decreasing mRNA expression was associated with increasing and decreasing cell proliferation in vitro. The presence of miRNA in two studies increased the sensitivity of the drug and exhibited a considerable growth inhibitory effect on cancer cell proliferation. The apoptotic rate was significantly increased in four studies by increased mRNA expression and reduced mrna expression. Tumor volume of xenograft models in three studies suppressed by antitumor miRNA activity. In contrast, anti-miRNA activity in one study decreased the tumor volume. Exosomal miRNAs can be regulators of chemo-resistance and predict adverse outcomes in CRC patients. In sum, exosomes containing miRNAs can be a promising biomarker for the prognosis and diagnosis of CRC. Subsequent research should be a focus on delineating the function of exosomal miRNA before clinical use.

Multiple interactions between melatonin and non-coding RNAs in cancer biology.

The melatonin hormone secreted by the pineal gland is involved in physiological functions such as growth and maturation, circadian cycles, and biological activities including antioxidants, anti-tumor, and anti-ischemia. Melatonin not only interacts with proteins but also has functional effects on regulatory RNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). In this study, we overview various physiological and pathological conditions affecting melatonin through lncRNA and miRNA. The information compiled herein will serve as a solid foundation to formulate ideas for future mechanistic studies on melatonin. It will also provide a chance to more clarify the emerging functions of the non-coding transcriptome.

The cross-talk between signaling pathways, noncoding RNAs and DNA damage response: Emerging players in cancer progression.

The DNA damage response (DDR) pathway's primary purpose is to maintain the genome structure's integrity and stability. A great deal of effort has done to understand the exact molecular mechanisms of non-coding RNAs, such as lncRNA, miRNAs, and circRNAs, in distinct cellular and genomic processes and cancer progression. In this regard, the ncRNAs possible regulatory role in DDR via modulation of key components expression and controlling repair signaling pathway activation is validated. Therefore, in this article, we will discuss the latest developments of ncRNAs contribution in different aspects of DNA repair through regulation of ATM-ATR, P53, and other regulatory signaling pathways.

The importance of co-delivery of nanoparticle-siRNA and anticancer agents in cancer therapy.

According to global statistics, cancer is the second leading cause of death worldwide. Because of the heterogeneity of cancer, single-drug therapy has many limitations due to low efficacy. Therefore, combination therapy with two or more therapeutic agents is being arisen. One of the most important approaches in cancer therapy is the shot down of key genes involved in apoptotic processes and cell cycle. In this regard, siRNA is a good candidate, a highly attractive method to suppressing tumor growth and invasion. Combination therapy with siRNAs and chemotherapeutic agents can overcome the multidrug resistance and increase apoptosis. The efficient delivery of siRNA to the target cell/tissue/organ has been a challenge. To overcome these challenges, the presence of suitable delivery systems by using nanoparticles is interesting. In this review, we discuss the current challenges for successful RNA interference. Also, we suggested proper a strategy for delivering siRNA that can be useful in targeting therapy. Finally, the combination of a variety of anticancer drugs and siRNA through acceptable delivery systems and their effects on cell cycle and apoptosis will be evaluated.

Shelterin Complex at Telomeres: Implications in Ageing.

Different factors influence the development and control of ageing. It is well known that progressive telomere shorting is one of the molecular mechanisms underlying ageing. The shelterin complex consists of six telomere-specific proteins which are involved in the protection of chromosome ends. More particularly, this vital complex protects the telomeres from degradation, prevents from activation of unwanted repair systems, regulates the activity of telomerase, and has a crucial role in cellular senescent and ageing-related pathologies. This review explores the organization and function of telomeric DNA along with the mechanism of telomeres during ageing, followed by a discussion of the critical role of shelterin components and their changes during ageing.

Stabilization of telomere by the antioxidant property of polyphenols: Anti-aging potential.

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.