-
Life Sciences Nov 2023Triple-Negative Breast Cancer (TNBC) is a highly aggressive and invasive type of breast cancer (BC) with high mortality rate wherein effective target medicaments are... (Review)
Review
Triple-Negative Breast Cancer (TNBC) is a highly aggressive and invasive type of breast cancer (BC) with high mortality rate wherein effective target medicaments are lacking. It is a very heterogeneous group with several subtypes that account for 10-20% of cancer among women globally, being negative for three most important receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)), with an early and high recurrence resulting in poor survival rate. Therefore, a more thorough knowledge on carcinogenesis of TNBC is required for the development of personalized treatment options. miRNAs can either promote or suppress tumorigenesis and have been linked to a number of features of cancer progression, including proliferation, metastasis, apoptosis, and epithelial-mesenchymal transition (EMT). Recent miRNA research shows that there is great potential for the development of novel biomarkers as they have emerged as drivers of tumorigenesis and provide opportunities to target various components involved in TNBC, thus helping to solve this difficult-to-treat disease. In this review, we summarize the most relevant miRNAs that play an essential role in TNBC biology. Their role with regard to molecular mechanisms underlying TNBC progression has been discussed, and their potential use as therapeutic or prognostic markers to unravel the intricacy of TNBC based on the pieces of evidence obtained from various works of literature has been briefly addressed.
Topics: Humans; Female; MicroRNAs; Triple Negative Breast Neoplasms; Carcinogenesis
PubMed: 37858714
DOI: 10.1016/j.lfs.2023.122183 -
Biomedicine & Pharmacotherapy =... Sep 2023MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have... (Review)
Review
MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have been demonstrated to act as key regulators in various pathophysiological processes and play significant roles in a wide range of human diseases, particularly cancer. Current research highlights the aberrant expression of microRNA-488 (miR-488) in multiple human diseases and its critical involvement in disease initiation and progression. Moreover, the expression level of miR-488 has been linked to clinicopathological features and patient prognosis across different diseases. However, a comprehensive systematic review of miR-488 is lacking. Therefore, our study aims to consolidate the current knowledge surrounding miR-488, with a primary focus on its emerging biological functions, regulatory mechanisms, and potential clinical applications in human diseases. Through this review, we aim to establish a comprehensive understanding of the diverse roles of miR-488 in the development of various diseases.
Topics: Humans; MicroRNAs; Neoplasms
PubMed: 37418982
DOI: 10.1016/j.biopha.2023.115115 -
Cells May 2024MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived... (Review)
Review
MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. : In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared to be involved in BDNF regulation by microRNAs. : Searches were conducted on PubMed.gov using the terms "BDNF" AND "MicroRNA" and "brain-derived neurotrophic factor" AND "MicroRNA", updated on 1 September 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and : The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF.
Topics: Brain-Derived Neurotrophic Factor; MicroRNAs; Humans; Animals; Gene Expression Regulation
PubMed: 38786102
DOI: 10.3390/cells13100880 -
Advanced Science (Weinheim,... Nov 2023Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved...
CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.
Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway-associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway-related intermediate metabolites and elevates NADP /NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR-212-5p to upregulate c-Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR-212-5p/c-Met axis plays a key role in oxidative pentose phosphate pathway-mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.
Topics: Humans; MicroRNAs; Colorectal Neoplasms; Pentose Phosphate Pathway; Liver Neoplasms; Oxidative Stress; Adipokines
PubMed: 37870214
DOI: 10.1002/advs.202205229 -
Gene Feb 2024Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA that plays important roles in the occurrence and development of various cancers. Current research... (Review)
Review
Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA that plays important roles in the occurrence and development of various cancers. Current research indicates that circRNA can inhibit the function of miRNA by acting as an miRNA sponge, interacting with proteins, and being translated into proteins. Most current research focuses on the circRNA-miRNA interaction; however, few studies have investigated the interaction between circRNAs and RNA binding proteins (RBPs) in breast cancer. In this review, we systematically summarize the potential molecular mechanism of the circRNA-protein interaction in breast cancer. Specifically, we elaborate on the direct interaction between circRNAs and proteins in breast cancer, including the functions of circRNA as protein sponges, decoys, and scaffolds, thereby affecting the progression of breast cancer. We also discuss the indirect interaction between circRNAs and proteins in breast cancer in which RBPs, transcription factors and m6A modifying enzymes could in turn regulate the expression and formation of circRNA. Finally, we discuss the potential application of circRNA-protein interaction for treating breast cancer, providing a reference for further research in this field.
Topics: Humans; Female; RNA, Circular; Breast Neoplasms; MicroRNAs
PubMed: 37984538
DOI: 10.1016/j.gene.2023.148019 -
Proceedings of the National Academy of... Oct 2023The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon...
The nuclear cleavage of a suboptimal primary miRNA hairpin by the Drosha/DGCR8 complex ("Microprocessor") can be enhanced by an optimal miRNA neighbor, a phenomenon termed cluster assistance. Several features and biological impacts of this new layer of miRNA regulation are not fully known. Here, we elucidate the parameters of cluster assistance of a suboptimal miRNA and also reveal competitive interactions amongst optimal miRNAs within a cluster. We exploit cluster assistance as a functional assay for suboptimal processing and use this to invalidate putative suboptimal substrates, as well as identify a "solo" suboptimal miRNA. Finally, we report complexity in how specific mutations might affect the biogenesis of clustered miRNAs in disease contexts. This includes how an operon context can buffer the effect of a deleterious processing variant, but reciprocally how a point mutation can have a nonautonomous effect to impair the biogenesis of a clustered, suboptimal, neighbor. These data expand our knowledge regarding regulated miRNA biogenesis in humans and represent a functional assay for empirical definition of suboptimal Microprocessor substrates.
Topics: Humans; MicroRNAs; RNA Processing, Post-Transcriptional; RNA-Binding Proteins; Ribonuclease III
PubMed: 37788316
DOI: 10.1073/pnas.2306727120 -
Aging Dec 2023Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of...
Response to oncogenic factors like UV, GADD45 family in skin participates in scavenging ROS, DNA repair and cell cycle control. Because of this, the previous study of the chronic UVB injury model has found that hsa-miR-300 can conduct intercellular transport by exosomes and target regulation of GADD45B. Whether the hsa-miR-300-GADD45B still regulates tumor development by cell cycle pathway is unclear. Through transcriptomic analysis of primary (n=39) and metastatic (n=102) melanoma, it was confirmed that in metastatic samples, some of the 97 down-regulated genes participate in maintaining skin homeostasis while 42 up-regulated genes were enriched in cancer-related functions. Furthermore, CDKN1A, CDKN2A, CXCR4 and RAD51 in the melanoma pathway, were also differentially expressed between normal skin and melanoma. CDKN1A and CDKN2A were also found to be involved in TP53-dependent cell cycle regulation. In conclusion, it was speculated that CDKN1A, CDKN2A, TP53, GADD45B and hsa-miR-300 may have regulatory relationships. It was demonstrated that there is a bidirectional regulation between hsa-miR-300 and TP53. In addition, miR-300 can regulate CDKN1A by GADD45B/TP53 and promote melanoma growth by accelerating the cell cycle transition from G1/S to G2 phase.
Topics: Humans; Melanoma; Cell Cycle; MicroRNAs; Cell Division; Cell Cycle Checkpoints; GADD45 Proteins; Antigens, Differentiation
PubMed: 38070141
DOI: 10.18632/aging.205276 -
International Journal of Oncology Jan 2024Non‑coding RNAs with a length of 22‑24 nt are known as microRNAs (miRNAs or miRs), which are critical regulators of protein translation. Over the past 10 years, the... (Review)
Review
Non‑coding RNAs with a length of 22‑24 nt are known as microRNAs (miRNAs or miRs), which are critical regulators of protein translation. Over the past 10 years, the roles of miRNAs have been extensively investigated in several human cancer types. There is evidence to indicate that miRNAs regulate gene expression by concentrating on a number of substances that have an impact on the physiology and development of cancer cells. Thus, miRNAs as regarded as effective targets for further studies on the design of novel therapeutic strategies. Hepatocellular carcinoma, breast, prostate, and ovarian cancer are only a few of the cancers that miR‑124 suppresses. Furthermore, it has been shown that miR‑124 is linked to the development and aggressive spread of malignancies. The aim of the present review was to clarify and highlight the role of miR‑124 in the development and progression of cancer, emphasizing recent research illustrating how miR‑124 has been used as a therapeutic agent against cancer, as well as the diagnostic potential, regulatory mechanisms and clinical application of miR‑124.
Topics: Male; Female; Humans; MicroRNAs; Ovarian Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 38038165
DOI: 10.3892/ijo.2023.5594 -
International Immunopharmacology Aug 2023Oxidative stress is a key pathogenic factor of cerebral ischemia/reperfusion (I/R) injury. MicroRNA-32-3p (miR-32-3p) plays critical roles in regulating ischemic...
Oxidative stress is a key pathogenic factor of cerebral ischemia/reperfusion (I/R) injury. MicroRNA-32-3p (miR-32-3p) plays critical roles in regulating ischemic diseases; however, its role in oxidative stress and cerebral I/R injury remains elusive. Primary cortical neurons and rats were treated with the agomir, antagomir and matched controls of miR-32-3p, and then received oxygen glucose deprivation/reperfusion (OGD/R) or I/R stimulation. To investigate the involvement of AMP-activated protein kinase (AMPK) and calcium-binding protein 39 (Cab39), a pharmacological inhibitor and small interfering RNA were used in vivo and in vitro. Herein, we found that miR-32-3p was upregulated in OGD/R-treated neurons and I/R-injured brains, and that inhibiting miR-32-3p by the miR-32-3p antagomir dramatically alleviated oxidative stress and neural death in OGD/R-stimulated primary cortical neurons. Conversely, overexpressing miR-32-3p by the miR-32-3p agomir further aggravated OGD/R-induced neural death and oxidative damage in primary cortical neurons. Meanwhile, we observed that the miR-32-3p antagomir prevented, while the miR-32-3p agomir facilitated neural death, oxidative damage and cerebral I/R injury in vivo. Mechanistically, miR-32-3p bound to the 3'-untranslated regions of Cab39, inhibited its protein level and subsequently inactivated AMPK. Conversely, treatment with the miR-32-3p antagomir upregulated Cab39 and activated AMPK, thereby attenuating oxidative damage and cerebral I/R injury. Moreover, inhibiting AMPK or Cab39 dramatically blocked the miR-32-3p antagomir-mediated beneficial effects against cerebral I/R injury in vivo and in vitro. miR-32-3p plays critical roles in neural death and oxidative damage upon I/R stimulation, and it is a novel target to treat cerebral I/R injury.
Topics: Rats; Animals; AMP-Activated Protein Kinases; MicroRNAs; Antagomirs; Reperfusion Injury; Brain Ischemia; Glucose; Apoptosis
PubMed: 37379707
DOI: 10.1016/j.intimp.2023.110504 -
Cellular Signalling Sep 2023Despite aggressive local and regional therapy, triple-negative breast cancer (TNBC) is characterized by an increased risk of locoregional recurrence. RNA-sequencing data...
BACKGROUND
Despite aggressive local and regional therapy, triple-negative breast cancer (TNBC) is characterized by an increased risk of locoregional recurrence. RNA-sequencing data has identified a large number of circRNAs in primary breast cancers, but the role of specific circRNAs in regulating the radiosensitivity of TNBC is not fully understood. This research aimed to investigate the function of circNCOR1 in the radiosensitivity of TNBC.
METHODS
CircRNA high-throughput sequencing was conducted on two breast cancer MDA-MB-231 and BT549 cell lines after 6 Gy radiation. The relationship between circNCOR1, hsa-miR-638, and CDK2 was determined by RNA immunoprecipitation (RIP), FISH and luciferase assays. The proliferation and apoptosis of breast cancer cells were measured by CCK8, flow cytometry, colony formation assays, and western blot.
RESULTS
Differential expression of circRNAs was closely related to the proliferation of breast cancer cells after irradiation. Overexpression of circNCOR1 facilitated the proliferation of MDA-MB-231 and BT549 cells and impaired the radiosensitivity of breast cancer cells. Additionally, circNCOR1 acted as a sponge for hsa-miR-638 to regulate the downstream target protein CDK2. Overexpression of hsa-miR-638 promoted apoptosis of breast cancer cells, while overexpression of CDK2 alleviated apoptosis and increased proliferation and clonogenicity. In vivo, overexpression of circNCOR1 partially reversed radiation-induced loosening of tumor structures and enhanced tumor cell proliferation.
CONCLUSION
Our results demonstrated that circNCOR1 bounds to hsa-miR-638 and targets CDK2, thereby regulating the radiosensitivity of TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; RNA, Circular; Cell Line, Tumor; MicroRNAs; Cell Proliferation; Gene Expression Regulation, Neoplastic; Apoptosis; Cell Movement; Cyclin-Dependent Kinase 2
PubMed: 37391048
DOI: 10.1016/j.cellsig.2023.110787