Durairaj Sekar

Expression and methylation of circulating microRNA-510 in essential hypertension

Hypertension (HTN) is one of the most common emerging disease in developing countries. It alters endothelial cell structure and function, resulting in several diseases, such as cardiovascular disease, peripheral vasculopathy, cerebrovascular disease and nephropathy. Although much progress has been made in researching HTN in recent years, early diagnosis and treatment of HTN are not yet satisfactory, and progression control/treatment is still poor. MicroRNAs are well-known regulators of the physiological and developmental processes of HTN. Our results revealed that miR-510 was upregulated in blood samples from HTN patients, whereas no significant differences were observed in the control samples. Methylation analyses corroborated the miR-510 upregulation in patient samples. These results suggested that miR-510 can be used as a novel biomarker for diagnosis and as a new therapeutic target for HTN.

MicroRNA21 and the various types of myeloid leukemia

Myeloid leukemia (ML) is heterogeneous cancer classified by abnormal growth of myeloid cells due to genetic aberrations and mutations. It is generally categorized by clonal disorders of hematopoietic stem cells and differentiation. The molecular mechanism behind the myeloid malignancies is not yet known, but recent sequencing analysis reveals all the mutated factors. As we know that there is currently no compromise on therapy for such types of malignancies and at the present painful process like chemotherapy and radiation therapy are not effective for the treatment of ML, so there is an urgent need to develop a non-invasive biomarker for different types of ML. MicroRNAs (MiRNAs) is a small non-coding RNAs that have been involved in a wide range of biological function and it is the main cause of the manifestation of many diseases. Among the reported MiRNAs, MIR-21 is considered to be an important MiRNA, which is frequently elevated in many types of types of cancer, suggesting that it plays an important role in cancer progressions. So far, there is no paper that signifies the role of miR-21 in all types of ML and the number of studies on the different category of ML is sparse. Therefore, the main thrust of this paper is to provide an overview of the current clinical evidence and significance of miR-21 in ML. It was found that MiR-21 was found to be normally upregulated in all types of ML, however, we summarize the important research findings surrounding the role of miR-21 in different types of ML.

In Silico Identification of Human miR 3654 and its Targets Revealed its Involvement in Prostate Cancer Progression

BACKGROUND MicroRNAs (miRNAs) are non-coding RNAs known to control a broad range of biological functions such as cellular proliferation, differentiation and programmed cell death. Recent reports showed that miRNAs can act as oncogenes or tumor suppressors, thereby, playing an important role in cancer initiation and progression. Moreover, we know that Expressed sequence tags (ESTs) are random single pass sequence reads, which displays the condition/tissue specific transcripts (coding and non-coding) of an organism. METHODS In the present study, we have applied the bioinformatics approach to identify miRNA from prostate cancer using EST resource and its expressions were analyzed by quantitative reverse transcription PCR (qRT-PCR). RESULTS Analysis of transcriptomics resource from the LNCaP cells revealed the presence of an EST encoding hsa-miR-3654. Presence of the premature candidate of miR-3654, demonstrates its expression in LNCaP cells. We further indentified that the expression level (Fold Induction) of miR-3654 in LNCaP was higher than the normal and androgen insensitive prostate cancer cell lines (PNT1A, PC-3). CONCLUSION we have identified the miR-3654 involved in prostate cancer progression using computational approach and hypothesized that the down regulation of miR-3654 could be responsible for a solid tumor to get cancer stem-like cell phenotype. Further studies are required to investigate the molecular mechanisms behind the STAT3 mediated miR-3654 repression and the associated metastasis.

Deciphering the role of microRNA 21 in cancer stem cells (CSCs)

Irrespective of positive developments of cancer treatment, the mortality due to various cancers remains high and the mechanisms of cancer initiation and the development also remains mysterious. As we know that microRNAs are considered to be a short noncoding RNA molecules consisting of 21–25 nucleotides (nt) in length and they silence their target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3′-untranslated (UTR) region and play a very important role in cancer biology. Recent evidences indicate that miR-21 is over expressed in cancer stem cells and plays a vital role in cell proliferation, apoptosis, and invasion. Even though an increased expression level of miR-21 has been observed in cancer stem cells, studies related to the role of miR-21 in cancer stem cells are limited. The main aim of this mini review is to explain the potency of miR-21 in various cancer stem cells (CSCs) and as a new target for therapeutic interventions of cancer progression.

Dissecting the role of miR-21 in different types of stroke

Stroke is an important neurological disease in which blood flow to the brain is interrupted and it is becoming an increasing non-communicable disease in developing countries. Current treatment options for stroke is modifying lifestyle practice, diabetes treatment, drugs, and other factors management, but yet no cure is available in sight for the disease, despite it requires new insight into the molecular and therapeutic targets. In general, MicroRNAs (miRNAs) are small noncoding RNAs considered as of greater biological importance and controls molecular signaling pathways in diabetic pathogenesis. Among the reported MiRNAs, MIR-21 is considered to be an important MiRNA, which is frequently elevated in many types of types of strokes, suggesting that it plays an important role in cell proliferation, and apoptosis. Until now, there is no research paper that signifying the role of miR-21 in all types of strokes and the number of studies on the different category of strokes is limited, so in this paper, we are highlighting the recent investigations related to the significance of miR-21 in different types of strokes based on the up-to-date reports. It was found that MiR-21 was found to be normally up and down regulated in all types of strokes, however; we summarize the important research findings related to the role of miR-21 in different types of strokes.

Comment on the potential role of microRNAs in hypertension

MicroRNAs (miRNAs) are small non-coding RNAs considered to be of great biological importance and control molecular signaling pathways in various types of hypertension [1]. In general, like classical genes, miRNAs originate from the nucleus and transported to the cytoplasm where they are processed and regulate messenger RNA (mRNA) of target genes by targeting the 3′-untranslated region (3′-UTR) to suppress gene expression [2]. miRNAs which are present in serum have the potential to serve as prognostic and diagnostic biomarkers. Interestingly, circulatory miRNAs can be used as non-invasive biomarkers for many diseases including cardiovascular diseases, cancer, diabetes, and strokes [3–5]. Hypertension is a chronic medical condition that is common among populations worldwide [6]. The occurrence of hypertension is increasing in developing countries and it is one of the most important causes of death in older persons. Hypertension results from a complex interaction of genetic and environmental factors [7]. In general, miRNAs control a wide range of cellular mechanisms such as stem cell maintenance, host–viral interaction, apoptosis, cell proliferation, and gene expression. Most importantly, they act as important gene expression regulators, and modulate cardiovascular development and disease progressions. They are emerging as potential biomarkers and therapeutic targets in hypertension and other related diseases [2]. In this context, a better understanding of miRNAs and their role in different types of hypertension is of great importance and may lead to the identification of new prognostic, diagnostic, or therapeutic targets [8]. Recently, our group published a research article on miR-510 and its role in essential hypertension [1]. In that study, we attempted to show that miR-510 is a candidate biomarker for essential hypertension and how methylation affects the expression of miR-510 and its targets. Interestingly, the article published in the current edition of Journal of Human Hypertension by Gamboa et al. has reported on the potential impact of miR-33 in hypertension [9]. MiR-33 has been found to be a key regulator in the initiation and progression of atherosclerosis but its role in arterial hypertension had not yet been investigated. Recent studies have shown that miR-21 plays roles in several types of hypertension [10–12], but validation of these results and more clinical trials are required to prove miR-21 is a therapeutic target for hypertension. The study by Gamboa et al. reports upregulation of miR-33a-5p and downregulation of miR-33a-3p in monocytes associated with hypertension. In addition, upregulation of miR-33a-5p in monocytes from Mexican hypertensive patients was associated with elevated carotid intima-media thickness and could therefore be involved in the development of atherosclerosis. More results and clinical data are needed to prove this concept and help define associations of miR-33a in hypertensive patients undergoing different medical treatments. Furthermore, there is no clear molecular mechanism to explain the upregulation of miR-33a-5p. More studies with larger sample sizes should help to elucidate the signal transduction pathways that surround miR-33a and its targets in hypertension.

Computational Identification of microRNA-17-3p in Breast Cancer Cells

BACKGROUND MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules involved in the RNA silencing and post-transcriptional regulation of gene expression. miRNAs are well conserved in both plants and animals, and are thought to be a vital and evolutionarily ancient component of gene regulation and also act as oncogenes or tumor suppressors. It is known that Express Sequence Tags (EST) are a short sub-sequence of cDNA sequence, which contain information of condition or tissue specific transcripts (coding and non-coding) of an organism. METHODS In the present study, we have applied the bioinformatics tools to identify miRNA from breast cancer using EST resource. Through bioinformatics approach, the presence of an EST encoding hsa-miR-17- 3p of breast cancer was identified. RESULTS Further studies reveal that hsa-miR-17 is confirmed in the breast cancer specific EST sequence among the predicted miRNAs secondary structure. Moreover, miR-17-3p could be responsible for a tumor suppression, which plays a major role in human breast cancer. CONCLUSION Further studies are required to investigate the molecular mechanisms behind miR-17-3p involves in the suppression of breast cancer cells. Interestingly, our target analysis suggesting that all the targets involved in multiple signaling pathways in different cell regulations moreover, we need to have more number of in vitro and in vivo studies that prove miR-17-3p as candidate microRNA for breast cancer cells.

Commentary: Role of MicroRNAs in HIV Related Studies

Micro RNAs (miRNAs) are well known regulatory factor of physiological and developmental processes, it has been revealed that many miRNAs contribute the initiation and progression of various cancers. Micro RNAs are being reported in body fluids, such as serum, plasma, and urine, and can be readily used as non-invasive biomarkers for various diseases and served as a novel diagnostic and prognostic tools.