Up-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer Survival

Abstract

BackgroundMicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.Methods and ResultsWe measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation.ConclusionsThe current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21.

Identification of miR-125a-5p as a tumor suppressor of renal cell carcinoma, regulating cellular proliferation, migration and apoptosis

“…MiRNAs have diverse functions and are involved in a variety of biochemical processes, including cellular differentiation, proliferation, apoptosis, metabolism and disease, including cancer (18). Deregulation of miRNAs is emerging as a major aspect of cancer etiology, and has previously been confirmed to be capable of promoting cancer initiation and progression in vivo (19), including in RCC.…”

“…Deregulation of miRNAs is emerging as a major aspect of cancer etiology, and has previously been confirmed to be capable of promoting cancer initiation and progression in vivo (19), including in RCC. Numerous miRNAs have been confirmed to be upregulated in RCC, including miR-21, miR-210 and miR-155 (18,19), while miR-127-3p, miR-145 and miR-126 have been shown to be significantly downregulated and correlated with relapse-free survival in patients with nonmetastatic RCC (20). Furthermore, serum miRNA levels have been associated with RCC and may be used as potential biomarkers; including miR-210 for early detection (19), miR-378 and miR-451 for diagnosis (21), and miR-122, miR-514, miR-192 and miR-215 for prognosis prediction and as therapeutic targets (18,22).…”

“…Numerous miRNAs have been confirmed to be upregulated in RCC, including miR-21, miR-210 and miR-155 (18,19), while miR-127-3p, miR-145 and miR-126 have been shown to be significantly downregulated and correlated with relapse-free survival in patients with nonmetastatic RCC (20). Furthermore, serum miRNA levels have been associated with RCC and may be used as potential biomarkers; including miR-210 for early detection (19), miR-378 and miR-451 for diagnosis (21), and miR-122, miR-514, miR-192 and miR-215 for prognosis prediction and as therapeutic targets (18,22). MiR-125a-5p has been described as a tumor suppressor in numerous human cancers (10)(11)(12)(13).…”

Investigation of nonspecific cross-reacting antigen 2 as a prognostic biomarker in bone marrow plasma from colorectal cancer patients

“…First, several exploratory studies performed on CRC cohorts failed to identify miR-21 as a prognostic biomarker, but instead other miRNAs, such as miR-17, miR-18a, miR-133b, miR-185, miR-22, miR-200c , miR-141, miR-221 and miR-150 were associated with overall survival [168,169,176,[199][200][201] [202,203]. Secondly, miR-21 is not tissue specific, as it is found to be overexpressed in several cancers including breast, lung and kidney [204][205][206].…”

“…MiR-21 is a highly studied oncogenic factor that targets several tumor suppressor genes in various model systems and has been found to be overexpressed in at least 18 malignancies indicating that altered expression of miR-21 is a common mechanism in carcinogenesis [193,[204][205][206]. MiRNA-21 is the most studied miRNA in CRC and was included in our study for its proposed association with advanced tumor stage and survival [158,166].…”