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E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C.

ABSTRACT: E2F1 (E2F transcription factor 1) can act as a tumor suppressor or oncogene. We report the molecular mechanism of E2F1 in ovarian carcinoma tumorigenesis and progression. E2F1 expression levels in ovarian carcinoma tissue were examined by immunohistochemistry. After E2F1 plasmid transfection and E2F1-microRNA-519d (miR-519d)/si-RhoC (Ras homolog gene family member C) co-transfection, ovarian cancer cell phenotypes and the related molecules were examined in vitro and in vivo. E2F1 was overexpressed in type I and type II ovarian carcinoma as compared to normal ovary tissues and normal fallopian tube tissues, respectively. E2F1 overexpression promoted cell proliferation, G1-S progression, survival, migration, and invasion in vitro; miR-519d or siRhoC co-transfection reversed E2F1 oncogenic effects. E2F1 overexpression promoted tumor growth in vivo; miR-519d overexpression inhibited it. E2F1 overexpression increased RhoC, Bcl-2, cyclin D1, survivin, MMP2 (matrix metalloproteinase 2), MMP9, STAT3 (signal transducer and activator of transcription 3), and HuR (ELAV-like RNA-binding protein 1) expression; miR-519d overexpression decreased their expression. E2F1 downregulated miR-519d directly and miR-519d downregulated RhoC directly. Conversely, miR-519d directly downregulated E2F1, There is a direct repressive regulatory loop between E2F1 and miR-519d. We provide evidence that E2F1/miR-519d/RhoC is a promising signaling pathway for diagnosing and treating ovarian carcinoma.

SUBMITTER: Sang XB

PROVIDER: S-EPMC5362443 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C.

Sang Xiu-Bo XB Zong Zhi-Hong ZH Wang Li-Li LL Wu Dan-Dan DD Chen Shuo S Liu Bo-Liang BL Zhao Yang Y

Oncotarget 20170201 9

E2F1 (E2F transcription factor 1) can act as a tumor suppressor or oncogene. We report the molecular mechanism of E2F1 in ovarian carcinoma tumorigenesis and progression. E2F1 expression levels in ovarian carcinoma tissue were examined by immunohistochemistry. After E2F1 plasmid transfection and E2F1-microRNA-519d (miR-519d)/si-RhoC (Ras homolog gene family member C) co-transfection, ovarian cancer cell phenotypes and the related molecules were examined in vitro and in vivo. E2F1 was overexpress ...[more]

PMID: 28146423

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Project description:BackgroundTo provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not. Here, we test whether tacrolimus-induced hypertension involves the RhoA (Ras homolog family member A)/ROCK (Rho-associated protein kinase) pathway in male C57Bl/6 mice.MethodsIntra-arterial blood pressure was measured under anesthesia. The reactivity of renal afferent arterioles and mesenteric arteries were assessed in vitro using microperfusion and wire myography, respectively.ResultsTacrolimus induced a transient rise in systolic arterial pressure that was blocked by the RhoA/ROCK inhibitor Fasudil (12.0±0.9 versus 3.2±0.7; P<0.001). Moreover, tacrolimus reduced the glomerular filtration rate, which was also prevented by Fasudil (187±20 versus 281±8.5; P<0.001). Interestingly, tacrolimus enhanced the sensitivity of afferent arterioles and mesenteric arteries to Ang II (angiotensin II), likely due to increased intracellular Ca2+ mobilization and sensitization. Fasudil prevented increased Ang II-sensitivity and blocked Ca2+ mobilization and sensitization. Preincubation of mouse aortic vascular smooth muscle cells with tacrolimus activated the RhoA/ROCK/MYPT-1 (myosin phosphatase targeting subunit 1) pathway. Further, tacrolimus increased cytoplasmic reactive oxygen species generation in afferent arterioles (107±5.9 versus 163±6.4; P<0.001) and in cultured mouse aortic vascular smooth muscle cells (100±7.5 versus 160±23.2; P<0.01). Finally, the reactive oxygen species scavenger Tempol inhibited tacrolimus-induced Ang II hypersensitivity in afferent arterioles and mesenteric arteries.ConclusionsThe RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing Ang II-specific vasoconstriction, and reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.

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E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C.

Publications

E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C.

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