The role of non-coding RNAs in diabetes-induced osteoporosis.

Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP. Recently, non-coding RNAs (ncRNAs) have received more attention due to their significant role in cellular functions and bone formation. It is worth noting that ncRNAs have also been demonstrated to participate in the progression of DOP. Meanwhile, nano-delivery systems are considered a promising strategy to treat DOP because of their cellular targeting, sustained release, and controlled release characteristics. Additionally, the utilization of novel technologies such as the CRISPR system has expanded the scope of available options for treating DOP. Hence, this paper explores the functions and regulatory mechanisms of ncRNAs in DOP and highlights the advantages of employing nanoparticle-based drug delivery techniques to treat DOP. Finally, this paper also explores the potential of ncRNAs as diagnostic DOP biomarkers.

Dysregulation of non-coding RNAs mediates cisplatin resistance in hepatocellular carcinoma and therapeutic strategies.

Hepatocellular carcinoma (HCC) is the fourth major contributor to cancer-related deaths worldwide, and patients mostly have poor prognosis. Although several drugs have been approved for the treatment of HCC, cisplatin (CDDP) is still applied in treatment of HCC as a classical chemotherapeutic drug. Unfortunately, the emergence of CDDP resistance has caused HCC patients to exhibit poor drug response. How to mitigate or even reverse CDDP resistance is an urgent clinical issue to be solved. Because of critical roles in biological functional processes and disease developments, non-coding RNAs (ncRNAs) have been extensively studied in HCC in recent years. Importantly, ncRNAs have also been demonstrated to be involved in the development of HCC to CDDP resistance process. Therefore, this review highlighted the regulatory roles of ncRNAs in CDDP resistance of HCC, elucidated the multiple potential mechanisms by which HCC develops CDDP resistance, and attempted to propose multiple drug delivery systems to alleviate CDDP resistance. Recently, ncRNA-based therapy may be a feasible strategy to alleviate CDDP resistance in HCC. Meanwhile, nanoparticles can overcome the deficiencies in ncRNA-based therapy and make it possible to reverse tumor drug resistance. The combined use of these strategies provides clues for reversing CDDP resistance and overcoming the poor prognosis of HCC.

Exploring the crosstalk between long non-coding RNAs and microRNAs to unravel potential prognostic and therapeutic biomarkers in ß-thalassemia.

ß-thalassemia is a prevalent monogenic disorder characterized by reduced or absent synthesis of the ß-globin chain. Although great effort has been made to ameliorate the disease severity of ß-thalassemic patients, progress has been stymied due to limited understanding of the detailed molecular mechanism of disease pathogenesis. Recently, non-coding RNAs have been established as key players in regulating various physiological and pathological processes. Many ncRNAs are involved in hematopoiesis and erythroid development. Furthermore, various studies have also reported the complex interplay between different ncRNAs, such as miRNA, lncRNAs, etc. in regulating disease progression and pathogenesis. Both lncRNAs and miRNAs have been identified as independent regulators of globin gene expression and are intricately involved in disease pathogenesis; yet accumulating evidence suggests that the cross-talk between lncRNAs and miRNAs is intricately involved in the underlying globin gene expression, fine-tuning the effect of their independent regulation. In this review, we summarize the current progress of research on the roles of lncRNAs and miRNAs implicated in ß-thalassemia disease, including their interactions and regulatory networks. This can provide important insights into the detailed epigenetic regulation of globin gene switching and has the potential to develop novel therapeutic approaches against ß-thalassemia.

The Role and Therapeutic Potential of Non-coding RNAs in Resistance to EGFR-TKIs targeted therapy for Non-small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most common type, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of NSCLC. EGFR-TKIs are known to develop a drug-resistant response after a certain number of cycles of dosing, and how to alleviate or even reverse EGFR-TKI resistance is an urgent problem at present. This review focuses on the role of ncRNAs in the resistance of NSCLC to EGFR-TKIs and the potential mechanisms underlying the development of NSCLC resistance to EGFR-TKIs. NcRNAs are involved in NSCLC resistance to EGFR-TKIs by mediating cellular drug efflux, epithelial-mesenchymal transition, apoptosis, autophagy, and EGFR mutation. ncRNAs play a crucial role in NSCLC resistance to EGFR-TKIs. Hopefully, the results will provide some guidance and help for the treatment and prognosis of NSCLC.

Regulatory Non-Coding RNAs in Familial Hypercholesterolemia, Theranostic Applications.

Familial hypercholesterolemia (FH) is a common monogenic disease which is associated with high serum levels of low-density lipoprotein cholesterol (LDL-C) and leads to atherosclerosis and cardiovascular disease (CVD). Early diagnosis and effective treatment strategy can significantly improve prognosis. Recently, non-coding RNAs (ncRNAs) have emerged as novel biomarkers for the diagnosis and innovative targets for therapeutics. Non-coding RNAs have essential roles in the regulation of LDL-C homeostasis, suggesting that manipulation and regulating ncRNAs could be a promising theranostic approach to ameliorate clinical complications of FH, particularly cardiovascular disease. In this review, we briefly discussed the mechanisms and pathophysiology of FH and novel therapeutic strategies for the treatment of FH. Moreover, the theranostic effects of different non-coding RNAs for the treatment and diagnosis of FH were highlighted. Finally, the advantages and disadvantages of ncRNA-based therapies vs. conventional therapies were discussed.

miRNA- and lncRNA-Based Therapeutics for Non-Hodgkin's Lymphoma: Moving towards an RNA-Guided Precision Medicine.

Increasing evidence has demonstrated the functional roles of miRNAs and lncRNAs in lymphoma onset and progression, either by acting as tumor-promoting ncRNAs or as tumor suppressors, emphasizing their appeal as lymphoma therapeutics. In fact, their intrinsic ability to modulate multiple dysregulated genes and/or signaling pathways makes them an attractive therapeutic approach for a multifactorial pathology like lymphoma. Currently, the clinical application of miRNA- and lncRNA-based therapies still faces obstacles regarding effective delivery systems, off-target effects, and safety, which can be minimized with the appropriate chemical modifications and the development of tumor site-specific delivery approaches. Moreover, miRNA- and lncRNA-based therapeutics are being studied not only as monotherapies but also as complements of standard treatment regimens to provide a synergic effect, improving the overall treatment efficacy and reducing the therapeutic resistance. In this review, we summarize the fundamentals of miRNA- and lncRNA-based therapeutics by discussing the different types of delivery systems, with a focus on those that have been investigated in lymphoma in vitro and in vivo. Moreover, we described the ongoing clinical trials of novel miRNA- and lncRNA-based therapeutics in lymphoma.