Current Molecular Medicine - Volume 23, Issue 7, 2023

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.

Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.

MicroRNAs (miRNAs) have been established as key players in various biological processes regulating differentiation, proliferation, inflammation, and autoimmune disorders. Emerging evidence suggests the critical role of miRNAs in the pathogenesis of multiple sclerosis (MS). Here, we provide a comprehensive overview of miRNAs, which are differentially expressed in MS patients or experimental autoimmune encephalomyelitis (EAE) mice and contribute to MS pathogenesis through regulating diverse pathways, including CD4+ T cells proliferation, differentiation, and activation in three subtypes of CD4+ T cells, including Th1, Th17 and regulatory T cells (Tregs). Moreover, the regulation of oligodendrocyte precursor cells (OPC) differentiation as a crucial player in MS pathogenesis is also described. Our literature research showed that miR-223 could affect different pathways involved in MS pathogenesis, such as promoting Th1 differentiation, activating the M2 phenotype of myeloid cells, and clearing myelin debris. MiR-223 was also identified as a potential biomarker, distinguishing relapsing-remitting multiple sclerosis (RRMS) from progressive multiple sclerosis (PMS), and thus, it may serve as an attractive target for further investigations. Our overview provides novel potential therapeutic targets for the treatment and new insights into miRNAs' role in MS pathogenesis.

Introduction: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. Materials and Methods: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. Results: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. Conclusion: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

Puberty is initiated from the continuous and growing pulsatile secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus and then the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Numerous factors involve pubertal initiation, whose abnormality may come from the dysfunction of these regulators. Makorin RING finger protein 3 (MKRN3) inhibits the secretion of GnRH and plays indispensable roles during the development of pubertal onset, and mutations of MKRN3 showed the commonest genetic cause of central precocious puberty (CPP). Recently, growing studies have revealed the functional mechanisms of MKRN3 in the pubertal initiation and the occurrence of CPP. In this review, we mainly summarized the research advances on the roles of MKRN3 in the development of pubertal onset and their underpinning mechanisms, contributing to a better understanding of the precise mechanisms of pubertal initiation and the pathogenesis of CPP.

Introduction: HERVs are human endogenous retroviruses, which represent about 8% of the human genome, and have various physiological functions, especially in pregnancy, embryo development and placenta formation. However, their involvement in diseases is not well defined. Some studies have observed changes in HERV expression according to age. Objective: Therefore, the aim of this systematic review was to analyze their role in pathogenesis and usage as diagnosis or prognosis biomarkers in aging disorders. Methods: In this study, a search on the Pubmed interface was performed for papers published from January 1953 to June 1^st, 2021. Results: 45 articles have been included, which matched the eligibility criteria and evaluated the following diseases: breast cancer, prostate cancer, amyotrophic lateral sclerosis (ALS), osteoarthritis, Alzheimer's disease, immuno-senescence, cognitive impairment, cataract, glaucoma and hypertension. Conclusion: In conclusion, the results suggested that HERVs play a role in the pathogenesis and can be used as biomarkers for the diagnosis or prognosis of aging disorders.

Background: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). Aims: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-β/Smad signaling pathway. Methods: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-β/Smad signaling pathway indexes were analyzed. Results: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-β/Smad signaling pathway-related indexes (TGF-β, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-β silencing, the TGF-β/Smad signaling pathway-related indicators (TGF-β, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-β +PL group than in the sh-TGF-β group. Conclusion: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-β/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.

Background: Angiogenesis of tumor cells is highly associated with tumorsecreted factors and matrix proteins. However, the underlying mechanism of tumorsecreted factors and matrix proteins during angiogenesis is rarely discussed. Objectives: This study investigated the relationship between the maternally expressed gene 3 (MEG3), a tumor-secreted growth factor, and Decorin, a tumor-secreted matrix protein, and evaluated their derivate roles in human endothelial cell development. Methods: Human endothelial cells were transiently transfected with a plasmid expressing antisense of Decorin mRNA (shDecorin) and silencing mRNA of MEG3 (siMEG3) or MEG3 over-expressive vectors. A series of qPCR and Western blot analysis was applied to characterize the expressions of MEG3 and Decorin in all transfected cells. Moreover, scratch, Transwell, and Matrigel neovascularization assays were performed to examine three key processes of endothelial cells' angiogenesis, including tubulogenesis, proliferation, and migratory levels. In addition, the cell viability was evaluated at each step via the MTT test. Results: The overexpression of MEG3 inhibited angiogenesis and migration of endothelial cells by preventing the expression of Decorin. At the same time, the inhibition of MEG3 via siRNA resulted in an increased expression of Decorin, enhanced tube formation levels, and promoted endothelial cell proliferation and migration. Furthermore, Decorin's knockdown suppressed the angiogenesis and migration of endothelial cells without affecting the expression of MEG3. Importantly, the stimulation of HUVEC cells with exogenous Decorin protein alleviated most phenotypes induced by the upregulation of MEG3. Conclusion: Our study demonstrated the anti-growth effects of MEG3 on vasculogenesis and migration of endothelial cells. Thus, by blocking the expression of Decorin in HUVECs, the overexpression of MEG3 repressed their development and might potentially alleviate the ischemic stroke.