Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches.

Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Video Abstract.

HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response.

High mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in the nucleus. Importantly, aberrant expression of HMGA2 occurs during carcinogenesis, and this protein is an upstream mediator of cancer hallmarks including evasion of apoptosis, proliferation, invasion, metastasis, and therapy resistance. HMGA2 targets critical signaling pathways such as Wnt/ß-catenin and mTOR in cancer cells. Therefore, suppression of HMGA2 function notably decreases cancer progression and improves outcome in patients. As HMGA2 is mainly oncogenic, targeting expression by non-coding RNAs (ncRNAs) is crucial to take into consideration since it affects HMGA2 function. MicroRNAs (miRNAs) belong to ncRNAs and are master regulators of vital cell processes, which affect all aspects of cancer hallmarks. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs), other members of ncRNAs, are upstream mediators of miRNAs. The current review intends to discuss the importance of the miRNA/HMGA2 axis in modulation of various types of cancer, and mentions lncRNAs and circRNAs, which regulate this axis as upstream mediators. Finally, we discuss the effect of miRNAs and HMGA2 interactions on the response of cancer cells to therapy. Regarding the critical role of HMGA2 in regulation of critical signaling pathways in cancer cells, and considering the confirmed interaction between HMGA2 and one of the master regulators of cancer, miRNAs, targeting miRNA/HMGA2 axis in cancer therapy is promising and this could be the subject of future clinical trial experiments.

Epigenetic regulation of autophagy by non-coding RNAs in gastrointestinal tumors: Biological functions and therapeutic perspectives.

Cancer is the manifestation of changes and mutations in genetic and epigenetic levels. Non-coding RNAs (ncRNAs) are commonly dysregulated in disease pathogenesis, and their role in cancer has been well-documented. The ncRNAs regulate various molecular pathways and mechanisms in cancer that can lead to induction/inhibition of carcinogenesis. Autophagy is a molecular "self-digestion" mechanism its function can be pro-survival or pro-death in tumor cells. The aim of the present review is to evaluate the role of ncRNAs in regulating autophagy in gastrointestinal tumors. The role of the ncRNA/autophagy axis in affecting the progression of gastric, liver, colorectal, pancreatic, esophageal, and gallbladder cancers is investigated. Both ncRNAs and autophagy mechanisms can function as oncogenic or onco-suppressor and this interaction can determine the growth, invasion, and therapy response of gastrointestinal tumors. ncRNA/autophagy axis can reduce/increase the proliferation of gastrointestinal tumors via the glycolysis mechanism. Furthermore, related molecular pathways of metastasis, such as EMT and MMPs, are affected by the ncRNA/autophagy axis. The response of gastrointestinal tumors to chemotherapy and radiotherapy can be suppressed by pro-survival autophagy, and ncRNAs are essential regulators of this mechanism. miRNAs can regulate related genes and proteins of autophagy, such as ATGs and Beclin-1. Furthermore, lncRNAs and circRNAs down-regulate miRNA expression via sponging to modulate the autophagy mechanism. Moreover, anti-cancer agents can affect the expression level of ncRNAs regulating autophagy in gastrointestinal tumors. Therefore, translating these findings into clinics can improve the prognosis of patients.

Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges.

Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt signaling contributes to proliferation, invasion, and inhibition of apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions with high prevalence of viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, and inflammation can also lead to initiation and development of HCC. The treatment of HCC depends on the identification of oncogenic factors that lead tumor cells to develop resistance to therapy. The present review article focuses on the role of PI3K/Akt signaling in HCC progression. Activation of PI3K/Akt signaling promotes glucose uptake, favors glycolysis and increases tumor cell proliferation. It inhibits both apoptosis and autophagy while promoting HCC cell survival. PI3K/Akt stimulates epithelial-to-mesenchymal transition (EMT) and increases matrix-metalloproteinase (MMP) expression during HCC metastasis. In addition to increasing colony formation capacity and facilitating the spread of tumor cells, PI3K/Akt signaling stimulates angiogenesis. Therefore, silencing PI3K/Akt signaling prevents aggressive HCC cell behavior. Activation of PI3K/Akt signaling can confer drug resistance, particularly to sorafenib, and decreases the radio-sensitivity of HCC cells. Anti-cancer agents, like phytochemicals and small molecules can suppress PI3K/Akt signaling by limiting HCC progression. Being upregulated in tumor tissues and clinical samples, PI3K/Akt can also be used as a biomarker to predict patients' response to therapy.

Graphene oxide nanoarchitectures in cancer therapy: Drug and gene delivery, phototherapy, immunotherapy, and vaccine development.

The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.

Gold nanostructure-mediated delivery of anticancer agents: Biomedical applications, reversing drug resistance, and stimuli-responsive nanocarriers.

The application of nanoarchitectures in cancer therapy seems to be beneficial for the delivery of antitumor drugs. In recent years, attempts have been made to reverse drug resistance, one of the factors threatening the lives of cancer patients worldwide. Gold nanoparticles (GNPs) are metal nanostructures with a variety of advantageous properties, such as tunable size and shape, continuous release of chemicals, and simple surface modification. This review focuses on the application of GNPs for the delivery of chemotherapy agents in cancer therapy. Utilizing GNPs results in targeted delivery and increased intracellular accumulation. Besides, GNPs can provide a platform for the co-delivery of anticancer agents and genetic tools with chemotherapeutic compounds to exert a synergistic impact. Furthermore, GNPs can promote oxidative damage and apoptosis by triggering chemosensitivity. Due to their capacity for providing photothermal therapy, GNPs can enhance the cytotoxicity of chemotherapeutic agents against tumor cells. The pH-, redox-, and light-responsive GNPs are beneficial for drug release at the tumor site. For the selective targeting of cancer cells, surface modification of GNPs with ligands has been performed. In addition to improving cytotoxicity, GNPs can prevent the development of drug resistance in tumor cells by facilitating prolonged release and loading low concentrations of chemotherapeutics while maintaining their high antitumor activity. As described in this study, the clinical use of chemotherapeutic drug-loaded GNPs is contingent on enhancing their biocompatibility.

STAT3 as a newly emerging target in colorectal cancer therapy: Tumorigenesis, therapy response, and pharmacological/nanoplatform strategies.

Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The therapeutic approaches for CRC encompass surgical intervention, chemotherapy, and radiotherapy. However, even with the implementation of these techniques, the 5-year survival rate for metastatic CRC remains at a mere 12-14%. In the realm of CRC treatment, gene therapy has emerged as a novel therapeutic approach. Among the crucial molecular pathways that govern tumorigenesis, STAT3 plays a significant role. This pathway is subject to regulation by cytokines and growth factors. Once translocated into the nucleus, STAT3 influences the expression levels of factors associated with cell proliferation and metastasis. Literature suggests that the upregulation of STAT3 expression is observed as CRC cells progress towards metastatic stages. Consequently, elevated STAT3 levels serve as a significant determinant of poor prognosis and can be utilized as a diagnostic factor for cancer patients. The biological and malignant characteristics of CRC cells contribute to low survival rates in patients, as the upregulation of STAT3 prevents apoptosis and promotes pro-survival autophagy, thereby accelerating tumorigenesis. Furthermore, STAT3 plays a role in facilitating the proliferation of CRC cells through the stimulation of glycolysis and promoting metastasis via the induction of epithelial-mesenchymal transition (EMT). Notably, an intriguing observation is that the upregulation of STAT3 can mediate resistance to 5-fluorouracil, oxaliplatin, and other anti-cancer drugs. Moreover, the radio-sensitivity of CRC diminishes with increased STAT3 expression. Compounds such as curcumin, epigallocatechin gallate, and other anti-tumor agents exhibit the ability to suppress STAT3 and its associated pathways, thereby impeding tumorigenesis in CRC. Furthermore, it is worth noting that nanostructures have demonstrated anti-proliferative and anti-metastatic properties in CRC.

Eco-friendly chitosan-based nanostructures in diabetes mellitus therapy: Promising bioplatforms with versatile therapeutic perspectives.

Nature-derived polymers, or biopolymers, are among the most employed materials for the development of nanocarriers. Chitosan (CS) is derived from the acetylation of chitin, and this biopolymer displays features such as biocompatibility, biodegradability, low toxicity, and ease of modification. CS-based nano-scale delivery systems have been demonstrated to be promising carriers for drug and gene delivery, and they can provide site-specific delivery of cargo. Owing to the high biocompatibility of CS-based nanocarriers, they can be used in the future in clinical trials. On the other hand, diabetes mellitus (DM) is a chronic disease that can develop due to a lack of insulin secretion or insulin sensitivity. Recently, CS-based nanocarriers have been extensively applied for DM therapy. Oral delivery of insulin is the most common use of CS nanoparticles in DM therapy, and they improve the pharmacological bioavailability of insulin. Moreover, CS-based nanostructures with mucoadhesive features can improve oral bioavailability of insulin. CS-based hydrogels have been developed for the sustained release of drugs and the treatment of DM complications such as wound healing. Furthermore, CS-based nanoparticles can mediate delivery of phytochemicals and other therapeutic agents in DM therapy, and they are promising compounds for the treatment of DM complications, including nephropathy, neuropathy, and cardiovascular diseases, among others. The surface modification of nanostructures with CS can improve their properties in terms of drug delivery and release, biocompatibility, and others, causing high attention to these nanocarriers in DM therapy.

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.

STAT3-EMT axis in tumors: Modulation of cancer metastasis, stemness and therapy response.

Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for metastasis of tumor cells and their spread to various organs and tissues of body, providing undesirable prognosis. In addition to migration, EMT increases stemness and mediates therapy resistance. Hence, pathways involved in EMT regulation should be highlighted. STAT3 is an oncogenic pathway that can elevate growth rate and migratory ability of cancer cells and induce drug resistance. The inhibition of STAT3 signaling impairs cancer progression and promotes chemotherapy-mediated cell death. Present review focuses on STAT3 and EMT interaction in modulating cancer migration. First of all, STAT3 is an upstream mediator of EMT and is able to induce EMT-mediated metastasis in brain tumors, thoracic cancers and gastrointestinal cancers. Therefore, STAT3 inhibition significantly suppresses cancer metastasis and improves prognosis of patients. EMT regulators such as ZEB1/2 proteins, TGF-ß, Twist, Snail and Slug are affected by STAT3 signaling to stimulate cancer migration and invasion. Different molecular pathways such as miRNAs, lncRNAs and circRNAs modulate STAT3/EMT axis. Furthermore, we discuss how STAT3 and EMT interaction affects therapy response of cancer cells. Finally, we demonstrate targeting STAT3/EMT axis by anti-tumor agents and clinical application of this axis for improving patient prognosis.

Crosstalk of miRNAs with signaling networks in bladder cancer progression: Therapeutic, diagnostic and prognostic functions.

Urological cancers are considered as life-threatening diseases around the world. Bladder cancer is one of the most malignant urological tumors with high mortality and morbidity. Bladder cancer is a heterogenous disease and genetic alterations have shown to be key players in regulating its progression. Although conventional therapies are somewhat beneficial in improving prognosis and survival, bladder cancer patients suffer from recurrence. MicroRNAs (miRNAs) are endogenous short RNA molecules that do not encode proteins and show dysregulated expression in human cancers. miRNAs are regulators of vital biological processes in cells such as proliferation, migration, differentiation and apoptosis. Dysregulation of miRNAs is observed in bladder cancer and they are used as biomarkers for diagnosis and prognosis of patients. LncRNAs and circRNAs are modulators of bladder cancer progression via miRNA expression regulation. Overexpression of onco-suppressor miRNAs impairs bladder cancer progression, while oncogenic miRNAs drive tumor progression. Glycolysis and EMT mechanisms are two important factors for proliferation and migration of bladder cancer that are modulated by miRNAs. Furthermore, miRNAs can affect STAT3 and Wnt/ß-catenin as instances of molecular factors in regulating bladder tumor progression. Bladder tumor response to drug therapy and radiotherapy is regulated by miRNAs. Hence, aim of current review is to provide function of miRNAs in bladder cancer based on their crosstalk with other molecular pathways and interaction with biological processes.

Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy.

Initiation and development of cancer depend on multiple factors that mutations in genes and epigenetic level can be considered as important drivers. Epigenetic factors include a large family of members and understanding their function in cancer has been a hot topic. LncRNAs are RNA molecules with no capacity in synthesis of proteins, and they have regulatory functions in cells. LncRNAs are localized in nucleus and cytoplasm, and their abnormal expression is related to development of tumor. This manuscript emphasizes on the role of lncRNA H19 in various cancers and its association with tumor hallmarks. The function of lncRNA H19 in most tumors is oncogenic and therefore, tumor cells increase its expression for promoting their progression. LncRNA H19 contributes to enhancing growth and cell cycle of cancers and by EMT induction, it is able to elevate metastasis rate. Silencing H19 induces apoptotic cell death and disrupts progression of tumors. LncRNA H19 triggers chemo- and radio-resistance in cancer cells. miRNAs are dually upregulated/down-regulated by lncRNA H19 in increasing tumor progression. Anti-cancer agents reduce lncRNA H19 in impairing tumor progression and increasing therapy sensitivity. A number of downstream targets and molecular pathways for lncRNA H19 have been detected in cancers including miRNAs, RUNX1, STAT3, ß-catenin, Akt2 and FOXM1. Clinical studies have revealed potential of lncRNA H19 as biomarker and its association with poor prognosis. LncRNA H19 can be transferred to cancer cells via exosomes in enhancing their progression.

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.

Ferroptosis contributes to the progression of female-specific neoplasms, from breast cancer to gynecological malignancies in a manner regulated by non-coding RNAs: Mechanistic implications.

Ferroptosis, a recently identified type of non-apoptotic cell death, triggers the elimination of cells in the presence of lipid peroxidation and in an iron-dependent manner. Indeed, ferroptosis-stimulating factors have the ability of suppressing antioxidant capacity, leading to the accumulation of reactive oxygen species (ROS) and the subsequent oxidative death of the cells. Ferroptosis is involved in the pathophysiological basis of different maladies, such as multiple cancers, among which female-oriented malignancies have attracted much attention in recent years. In this context, it has also been unveiled that non-coding RNA transcripts, including microRNAs, long non-coding RNAs, and circular RNAs have regulatory interconnections with the ferroptotic flux, which controls the pathogenic development of diseases. Furthermore, the potential of employing these RNA transcripts as therapeutic targets during the onset of female-specific neoplasms to modulate ferroptosis has become a research hotspot; however, the molecular mechanisms and functional alterations of ferroptosis still require further investigation. The current review comprehensively highlights ferroptosis and its association with non-coding RNAs with a focus on how this crosstalk affects the pathogenesis of female-oriented malignancies, from breast cancer to ovarian, cervical, and endometrial neoplasms, suggesting novel therapeutic targets to decelerate and even block the expansion and development of these tumors.

Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.

BACKGROUND: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. SCOPE OF REVIEW: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. MAJOR CONCLUSIONS: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

Nanostructures for site-specific delivery of oxaliplatin cancer therapy: Versatile nanoplatforms in synergistic cancer therapy.

As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.

Non-coding RNA-Mediated N6-Methyladenosine (m6A) deposition: A pivotal regulator of cancer, impacting key signaling pathways in carcinogenesis and therapy response.

The emergence of RNA modifications has recently been considered as critical post-transcriptional regulations which governed gene expression. N6-methyladenosine (m6A) modification is the most abundant type of RNA modification which is mediated by three distinct classes of proteins called m6A writers, readers, and erasers. Accumulating evidence has been made in understanding the role of m6A modification of non-coding RNAs (ncRNAs) in cancer. Importantly, aberrant expression of ncRNAs and m6A regulators has been elucidated in various cancers. As the key role of ncRNAs in regulation of cancer hallmarks is well accepted now, it could be accepted that m6A modification of ncRNAs could affect cancer progression. The present review intended to discuss the latest knowledge and importance of m6A epigenetic regulation of ncRNAs including mircoRNAs, long non-coding RNAs, and circular RNAs, and their interaction in the context of cancer. Moreover, the current insight into the underlying mechanisms of therapy resistance and also immune response and escape mediated by m6A regulators and ncRNAs are discussed.

Shedding light on function of long non-coding RNAs (lncRNAs) in glioblastoma.

The brain tumors and especially glioblastoma, are affecting life of many people worldwide and due to their high mortality and morbidity, their treatment is of importance and has gained attention in recent years. The abnormal expression of genes is commonly observed in GBM and long non-coding RNAs (lncRNAs) have demonstrated dysregulation in this tumor. LncRNAs have length more than 200 nucleotides and they have been located in cytoplasm and nucleus. The current review focuses on the role of lncRNAs in GBM. There two types of lncRNAs in GBM including tumor-promoting and tumor-suppressor lncRNAs and overexpression of oncogenic lncRNAs increases progression of GBM. LncRNAs can regulate proliferation, cell cycle arrest and metastasis of GBM cells. Wnt, STAT3 and EZH2 are among the molecular pathways affected by lncRNAs in GBM and for regulating metastasis of GBM cells, these RNA molecules mainly affect EMT mechanism. LncRNAs are involved in drug resistance and can induce resistance of GBM cells to temozolomide chemotherapy. Furthermore, lncRNAs stimulate radio-resistance in GBM cells. LncRNAs increase PD-1 expression to mediate immune evasion. LncRNAs can be considered as diagnostic and prognostic tools in GBM and researchers have developed signature from lncRNAs in GBM.

NF-ĸB axis in diabetic neuropathy, cardiomyopathy and nephropathy: A roadmap from molecular intervention to therapeutic strategies.

Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.