Restoring of miR-193a-5p Sensitizes Breast Cancer Cells to Paclitaxel through P53 Pathway.

Purpose: Recent evidence presented the important role of microRNAs in health and disease particularly in human cancers. Among those, miR-193 family contributes as a tumor suppressor in different benign and malignant cancers like breast cancer (BC) via interaction with specific targets. On the other hand, it was stated that miR-193 is able to modulate some targets in chemoresistant cancer cells. Therefore, the aim of this study was to evaluate the potential function of miR-193a-5p and paclitaxel in the apoptosis induction by targeting P53 in BC cells. Methods: At first, miR-193a-5p mimics were transfected to MDA-MB-231 BC cell line which indicated the lower expression level of miR-193a-5p. Subsequently, the transfected cells were treated with paclitaxel. Then, cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry and DAPI staining, and scratch-wound motility assays, respectively. Moreover, the expression levels of P53 was evaluated by qRT-PCR. Results: The expression level of miR-193a-5p was restored in MDA-MB-231 cells which profoundly inhibited the proliferation (P<0.0001), induced apoptosis (P <0.0001) and harnessed migration (P <0.0001) in the BC cells and more effectiveness was observed in combination with paclitaxel. Interestingly, increased miR-193a-5p expression led to a reduction in P53 mRNA, offering that it can be a potential target of miR-193a. Conclusion: Taken together, it is concluded that the combination of miR-193a-5p restoration and paclitaxel could be potentially considered as an effective therapeutic strategy to get over chemoresistance during paclitaxel chemotherapy.

Targeting ROCK signaling in health, malignant and non-malignant diseases.

A Rho-associated coiled-coil kinase (ROCK) is identified as a critical downstream effector of GTPase RhoA which contains two isoforms, ROCK1 (also known as p160ROCK and ROKß) and ROCK2 (also known as Rho-kinase and ROKα), the gene of which is placed on chromosomes 18 (18q11.1) and 2 (2p24), respectively. ROCKs have a principal function in the generation of actin-myosin contractility and regulation of actin cytoskeleton dynamics. They represent a chief role in regulating various cellular functions, such as apoptosis, growth, migration, and metabolism through modulation of cytoskeletal actin synthesis, and cellular contraction through phosphorylation of numerous downstream targets. Emerging evidence has indicated that ROCKs present a significant function in cardiac physiology. Of note, dysregulation of ROCKs involves in several cardiac pathological processes like cardiac hypertrophy, cardiac fibrosis, systemic blood pressure disorder, and pulmonary hypertension. Moreover, ROCKs, in addition to their role in regulating renal arteriolar contraction, glomerular blood flow, and filtration, can also play a role in controlling podocytes, tubular cells, and mesangial cell structure and function. Hyperactivity disorder and over-gene expression of Rho/ROCK have been indicated in different cancers. Furthermore, it seems that increasing the expression of mRNA or ROCK protein has an undesirable effect on patient survival and has a positive impact on the progression and worsening of disease prognosis. This review focuses on the physiological and pathological functions of ROCKs with a particular view on its possible value of ROCK inhibitors as a new therapy in cancers and non-cancer diseases.

A comprehensive review on miR-451: A promising cancer biomarker with therapeutic potential.

MicroRNAs (miRNAs) are proposed as a family of short noncoding molecules able to manage and control the expression of the gene targets at the posttranscriptional level. They contribute in several fundamental physiological mechanisms as well as a verity of human and animal diseases such as cancer progression. Among these tiny RNAs, miR-451 placed on chromosome 17 at 17q11.2 presents an essential role in many biological processes in health condition and also in pathogenesis of different diseases. Besides, it has been recently considered as a valuable biomarker for cancer detection, prognosis and treatment. Therefore, this review will provide the critical functions of miR-451 on biological mechanisms including cell cycle and proliferation, cell survival and apoptosis, differentiation and development as well as disease initiation and progression such as tumor formation, migration, invasion, and metastasis.

miR-193: A new weapon against cancer.

microRNAs (miRNAs) are known as a large group of short noncoding RNAs, which structurally consist of 19-22 nucleotides in length and functionally act as one of the main regulators of gene expression in important biological and physiological contexts like cell growth, apoptosis, proliferation, differentiation, movement (cell motility), and angiogenesis as well as disease formation and progression importantly in cancer cell invasion, migration, and metastasis. Among these notable tiny molecules, many studies recently presented the important role of the miR-193 family comprising miR-193a-3p, miR-193a-5p, miR-193b-3p, and miR-193b-5p in health and disease biological processes by interaction with special targeting and signaling, which mainly contribute as a tumor suppressor. Therefore, in the present paper, we review the functional role of this miRNA family in both health and disease conditions focusing on various tumor developments, diagnoses, prognoses, and treatment.

Key microRNAs in the biology of breast cancer; emerging evidence in the last decade.

microRNAs (miRNAs) are a family of small noncoding RNAs that play a pivotal role in the regulation of main biological and physiological processes, including cell cycle regulation, proliferation, differentiation, apoptosis, stem cell maintenance, and organ development. Dysregulation of these tiny molecules has been related to different human diseases, such as cancer. It has been estimated that more than 50% of these noncoding RNA sequences are placed on fragile sites or cancer-associated genomic regions. After the discovery of the first specific miRNA signatures in breast cancer, many studies focused on the involvement of these small RNAs in the pathophysiology of breast tumors and their possible clinical implications as reliable prognostic biomarkers or as a new therapeutic approach. Therefore, the present review will focus on the recent findings on the involvement of miRNAs in the biology of breast cancer associated with their clinical implications.

Dysregulation of key microRNAs in pancreatic cancer development.

Pancreatic cancer (PC) is mentioned as one of the fourth major cause of cancer-related deaths and also is considered as one of the most malignancies worldwide. Sadly, widely metastasis is frequently observed at the time of PC detection and there are, thereby, almost poor prognosis and ineffective treatment in PC patients. microRNAs (miRNAs), a group of short non-coding RNAs, regulate various cellular and developmental mechanisms, such as cell growth, proliferation, apoptosis, differentiation and angiogenesis. Also, they have essential roles even on the progression of different human and animal diseases. In recent years, extensive studies confirmed the important role of miRNAs in various steps of PC developments, including; tumor initiation, invasion and metastasis, which can use valuably for cancer detection, prognosis and therapy. Therefore, the present study reviewed the new recent investigations in miRNAs involvement in the biology of PC associated with their clinical implications.