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.

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.