Graphene oxide nanoarchitectures in cancer biology: Nano-modulators of autophagy and apoptosis.

Nanotechnology is a growing field, with many potential biomedical applications of nanomedicine for the treatment of different diseases, particularly cancer, on the horizon. Graphene oxide (GO) nanoparticles can act as carbon-based nanocarriers with advantages such as a large surface area, good mechanical strength, and the capacity for surface modification. These nanostructures have been extensively used in cancer therapy for drug and gene delivery, photothermal therapy, overcoming chemotherapy resistance, and for imaging procedures. In the current review, we focus on the biological functions of GO nanoparticles as regulators of apoptosis and autophagy, the two major forms of programmed cell death. GO nanoparticles can either induce or inhibit autophagy in cancer cells, depending on the conditions. By stimulating autophagy, GO nanocarriers can promote the sensitivity of cancer cells to chemotherapy. However, by impairing autophagy flux, GO nanoparticles can reduce cell survival and enhance inflammation. Similarly, GO nanomaterials can increase ROS production and induce DNA damage, thereby sensitizing cancer cells to apoptosis. In vitro and in vivo experiments have investigated whether GO nanomaterials show any toxicity in major body organs, such as the brain, liver, spleen, and heart. Molecular pathways, such as ATG, MAPK, JNK, and Akt, can be regulated by GO nanomaterials, leading to effects on autophagy and apoptosis. These topics are discussed in this review to shed some lights towards the biomedical potential of GO nanoparticles and their biocompatibility, paving the way for their future application in clinical trials.

Biological functions and molecular interactions of Wnt/ß-catenin in breast cancer: Revisiting signaling networks.

Changes in lifestyle such as physical activity and eating habits have been one of the main reasons for development of various diseases in modern world, especially cancer. However, role of genetic factors in initiation of cancer cannot be ignored and Wnt/ß-catenin signaling is such factor that can affect tumor progression. Breast tumor is the most malignant tumor in females and it causes high mortality and morbidity around the world. The survival and prognosis of patients are not still desirable, although there have been advances in introducing new kinds of therapies and diagnosis. The present review provides an update of Wnt/ß-catenin function in breast cancer malignancy. The upregulation of Wnt is commonly observed during progression of breast tumor and confirms that tumor cells are dependent on this pathway Wnt/ß-catenin induction prevents apoptosis that is of importance for mediating drug resistance. Furthermore, Wnt/ß-catenin signaling induces DNA damage repair in ameliorating radio-resistance. Wnt/ß-catenin enhances proliferation and metastasis of breast tumor. Wnt/ß-catenin induces EMT and elevates MMP expression. Furthermore, Wnt/ß-catenin participates in tumor microenvironment remodeling and due to its tumor-promoting factor, drugs for its suppression have been developed. Different kinds of upstream mediators Wnt/ß-catenin signaling in breast cancer have been recognized that their targeting is a therapeutic approach. Finally, Wnt/ß-catenin can be considered as a biomarker in clinical trials.

Long non-coding RNA/epithelial-mesenchymal transition axis in human cancers: Tumorigenesis, chemoresistance, and radioresistance.

Epithelial-to-mesenchymal transition (EMT) is a process that involves the transformation of polarized epithelial cells to attain a mesenchymal phenotype that presents an elevated migratory potential, invasiveness, and antiapoptotic properties. Many studies have demonstrated that EMT is a prominent event that is associated with embryogenesis, tumor progression, metastasis, and therapeutic resistance. The EMT process is driven by key transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and several long non-coding RNAs (lncRNAs) in many non-pathological as well as pathological conditions. In the present report, we have comprehensively discussed the oncogenic and tumor suppressor role of lncRNAs and their mechanism of action in the regulation of the EMT process in various cancers such as brain tumors, gastrointestinal tumors, and gynecological and urological tumors. We have also elaborated on the role of lncRNAs in the regulation of EMT-related transcription factors (such as Snail, Twist, ZEB, and TGF-ß) and therapeutic response (chemoresistance and radioresistance). Lastly, we have emphasized the role of exosomal lncRNAs in the regulation of EMT, metastasis, and therapeutic response in the aforementioned cancers. Taken together, this review provides a detailed insight into the understanding of role of lncRNAs/exosomal lncRNAs in EMT, metastasis, and therapeutic response in human cancers.

Non-coding RNAs targeting notch signaling pathway in cancer: From proliferation to cancer therapy resistance.

Cancer is a challenging to treat disease with a high mortality rate worldwide, nevertheless advances in science has led to a decrease in the number of death cases caused by cancer. Aberrant expression of genes occurs during tumorigenesis therefore targeting the signaling pathways that regulate these genes' expression is of importance in cancer therapy. Notch is one of the signaling pathways having interactions with other vital cell signaling molecules responsible for cellular functions such as proliferation, apoptosis, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), angiogenesis, and immune evasion. Furthermore, the Notch pathway is involved in response to chemo- and radiotherapy. Thus, targeting the Notch signaling pathway in cancer therapy can be beneficial for overcoming the therapeutic gaps. Non-coding RNAs (ncRNAs) are a class of RNAs that include short ncRNAs (such as micro RNAs) and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are ~22 nucleotides in length while lncRNAs have more than 200 nucleotides. Both miRNAs and lncRNAs control vital cellular mechanisms in cells and affect various signaling pathways and Notch is among them. The current review aims to discuss the critical role of ncRNAs in the regulation of the Notch signaling pathway by focusing on different cancer hallmarks including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.