Effect of the Protein Kinase B (PKB) Gene on the Carcinogenesis of Oral Squamous Cell Carcinoma in the South Indian Population.

INTRODUCTION: The most common head and neck cancer is oral squamous cell carcinoma (OSCC). It is also one of the most prevalent forms of cancer globally. The current pharmacological treatment strategy for oral cancer lacks specificity and is capable of causing various side effects. This fact highlights the increasing need for targeted therapy. Interestingly, protein kinase B (PKB), commonly referred to as the AKT serine/threonine kinase, is an oncogenic protein that controls cell development, proliferation, apoptosis, and glycogen metabolism. Thus, the present study analyzed the AKT gene expression in OSCC patient samples. MATERIALS AND METHODS: A total of 25 OSCC tissue samples and normal tissue samples were collected from the patients who reported to the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals in Chennai, India. The tissues were processed for H&E staining for histopathological confirmation, and expression studies of the AKT gene were done on both healthy and proven OSCC tissue samples. The data were shown as mean ± standard deviation, and p<0.05* was considered to be statistically significant. RESULTS: The quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the AKT gene had been significantly upregulated in the OSCC tissue samples when compared to normal tissues (p<0.05). Moreover, upregulated AKT is postulated to be involved in increased cell proliferation and reduced apoptosis in OSCC. CONCLUSION: The gene expression analysis was done in the samples of histologically confirmed OSCC, and it revealed that the AKT gene was significantly upregulated in OSCC tissues. Thus, AKT could be postulated as a potential therapeutic target for OSCC.

MicroRNA-510-3p regulated vascular dysfunction in Preeclampsia by targeting Vascular Endothelial Growth Factor A (VEGFA) and its signaling axis.

INTRODUCTION: Preeclampsia (PE) is a pregnancy complication associated with multi-organ damage and vascular dysfunction. Meanwhile, microRNAs or miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in the PE patients' blood compared to normal. Hence, we hypothesize that miR-510-3p targets Vascular endothelial growth factor A (VEGFA) in the regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential therapeutic target for PE. METHODS: The proliferation, migration, and apoptosis of HTR8/SVNeo and BeWo cells were analyzed by manipulating the miR-510-3p and VEGFA expression. Similarly, the inhibition of miR-510-3p through anti-miR-510-3p was analyzed in PE rat models, and the biochemical, hemodynamic parameters, and histopathology were examined between the groups. Moreover, the expression of miR-510-3p and VEGFA/PI3K/AKT/eNOS/mTOR axis was analyzed using qRT-PCR and Western blot. RESULTS: Significant changes were observed in the BP, proteinuria, and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets VEGFA leading to vascular dysfunction in PE, while treatment with anti-miR-510-3p in the PE-induced rat model exhibits a significant change in the expression of miR-510-3p/VEGFA/PI3K/AKT/eNOS/mTOR signaling where miR-510-3p showed lesser expression and vice versa with VEGFA. The gene and protein expression analysis revealed a significant correlation between miR-510-3p and the VEGFA signaling axis in PE. DISCUSSION: Thus, our findings from in vitro and in vivo suggest miR-510-3p as a potential therapeutic target and anti-miR-510-3p as a novel therapeutic molecule for PE.

MicroRNAs as important players in regulating cancer through PTEN/PI3K/AKT signalling pathways.

Cancer being the leading cause of mortality has become a great threat worldwide. Current cancer therapeutics lack specificity and have side effects due to a lack of understanding of the molecular mechanisms and signalling pathways involved in carcinogenesis. In recent years, researchers have been focusing on several signalling pathways to pave the way for novel therapeutics. The PTEN/PI3K/AKT pathway is one of the important pathways involved in cell proliferation and apoptosis, leading to tumour growth. In addition, the PTEN/PI3K/AKT axis has several downstream pathways that could lead to tumour malignancy, metastasis and chemoresistance. On the other hand, microRNAs (miRNAs) are important regulators of various genes leading to disease pathogenesis. Hence studies of the role of miRNAs in regulating the PTEN/PI3K/AKT axis could lead to the development of novel therapeutics for cancer. Thus, in this review, we have focused on various miRNAs involved in the carcinogenesis of various cancer via the PTEN/PI3K/AKT axis.

Diagnostic and Therapeutic Application of Exosomal microRNAs Inducing Inflammation in Type 2 Diabetes Mellitus.

Diabetes mellitus is a class of noncommunicable chronic metabolic disorders marked by hyperglycemia due to insulin production, insulin action or both and has reached epidemic levels around the world. The two most frequent types of diabetes are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Despite substantial improvements in the knowledge and treatment of DM, the associated incidence and mortality rates remain steadily increased. Reliable markers for the early detection, monitoring and focused treatment of DM are desperately required. Conversely, microRNAs (miRNAs) have received much significance due to their regulatory involvement in gene expression. Fascinatingly, exosomes can be enclosed into miRNAs to transport or distribute them into the target cells or tissues in which they have a physiological regulatory action. Thus, exosomal miRNAs are proving to be important regulators in the establishment and maintenance of DM, however, further mode of action will be needed to investigate in order to fully comprehend the pathophysiological process. Hereby, this review outlines the recent findings on the role of exosomal miRNAs intending to understand the precise function in diagnostic and therapeutic aspects in T2DM disease.

The role of microRNAs on the pathogenesis, diagnosis and management of portal hypertension in patients with chronic liver disease.

INTRODUCTION: Portal hypertension (PH) is the elevated pressure in the portal vein, which results in poor functioning of the liver and is influenced by various factors like liver cirrhosis, nonalcoholic fatty liver disease, schistosomiasis, thrombosis, and angiogenesis. Though the diagnosis and treatment have been advanced, early diagnosis of the disease remains a challenge, and the diagnosis methods are often invasive. Hence, the clear understanding of the molecular mechanisms of PH can give rise to the development of novel biomarkers which can pave way for early diagnosis in noninvasive methods, and also the identification of target genes can elucidate an efficient therapeutic target. AREAS COVERED: PubMed and Embase database was used to search articles with search terms 'Portal Hypertension' or 'pathophysiology' and 'diagnosis' and 'treatment' or "role of miRNAs in portal hypertension. EXPERT OPINION: Interestingly, biomarkers like microRNAs (miRNAs) have been studied for their potential role in various diseases including hypertension. In recent years, miRNAs have been proved to be an efficient biomarker and therapeutic target and few studies have assessed the roles of miRNAs in PH. The present paper highlights the potential roles of miRNAs in PH.

MicroRNAs in the epigenetic regulation of disease progression in Parkinson's disease.

Parkinson's disease (PD) is a multifactorial neurodegenerative condition with symptoms such as resting tremor, rigidity, bradykinesia (slowness of moment), and postural instability. Neuroinflammation plays a significant part in the onset and progression of neurodegeneration in a wide range of disorders, including PD. The loss of dopaminergic neurons in the substantia nigra (SN) is thought to be the primary cause of PD disease progression. However, other neurotransmitter systems like serotoninergic, glutamatergic, noradrenergic, adrenergic, cholinergic, tryptaminergic, and peptidergic appear to be affected as well. Epigenetic regulation of gene expression is emerging as an influencing factor in the pathophysiology of PD. In recent years, epigenetic regulation by microRNAs (miRNAs) has been discovered to play an important function in the disease progression of PD. This review explores the role of miRNAs and their signaling pathways in regulating gene expression from development through neurodegeneration and how these mechanisms are linked to the pathophysiology of PD, emphasizing potential therapeutic interventions.

CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer.

BACKGROUND: Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. MAIN TEXT: Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of "one-size-fits-all" therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. CONCLUSION: With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine.

Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer.

BACKGROUND: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.