Senescence-associated microRNAs linked to tumorigenesis

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

“…In this study, Dicer-induced senescence was relayed by mechanisms different to those shown here, which involved DNA damage and Arf-dependent activation of p53 (Mudhasani et al, 2008). Conflicting recent reports suggest that siRNA-mediated silencing of Dicer can trigger senescent markers in human fibroblasts (Srikantan et al, 2011) but it can also favor bypass of oncogene-induced senescence (Francia et al, 2012). It is well established that Dicer has functions independent from the canonical miRNA machinery, including heterochromatin formation, and production of noncanonical miRNA (Winter et al, 2009).…”

Metformin lowers the threshold for stress-induced senescence: A role for the microRNA-200 family and miR-205

“…Several studies have revealed that a variety of miRNAs are also differentially regulated during replicative senescence of human fibroblasts; [67][68][69][70] importantly, senescent fibroblasts appear to express distinct collections of miRNAs that play a central role in the senescence-elicited tumor suppression. 71 Because miRNAs extensively studied in the EMT of cancer cells (e.g., miR-200 family) [72][73][74][75] have recently been involved in the oxidative stress signature that regulates cellular senescence and tumorigenesis, 76,77 we decided to survey whether EMT-related miRNAs were differentially expressed in dividing (early-passage) HDFs compared with late-passage fibroblasts that had suffered an accelerated replicative senescence due to chronic exposure to metformin. Total RNA from "young," "old" and "metformin-treated" BJ-1 fibroblasts was evaluated using a customized array for quantitative, real-time PCR (qRT-PCR) of 12 miRNAs functionally associated with EMT and the reciprocal mesenchymal-to-epithelial transition (MET), namely miR-31, miR-21, miR-10b, miR-103, miR-9, let-7a, miR-200a, miR-205, miR-200c, miR-141, miR-155 and miR-429.…”

“…Plates were processed in an Applied Biosystems 7500 Fast Real-Time PCR System (Applied BiosystemsA) using automated baseline and threshold cycle detection. Data were explain the counterintuitive finding that chronic exposure of HDFs to metformin-similarly to oxidative stress exposuresignificantly upregulate the expression of the oncomiR miR-141, which reduces the production of pro-apoptotic and tumor-suppressor proteins, 114 and it has been found to decrease in senescence populations of fibroblasts, 71 thus following a pattern of miRNA expression mirroring the expression needed to suppress tumorigenesis. Mateescu's suggestion that ROS-enhanced expression of miR-200s promotes the generation of "stressed" tumor cells that become sensitized to ulterior stresses 77,113 notably agrees with our recent suggestion that the bioenergetic crisis imposed by metformin, which may involve enhanced oxidative stress, can allow an accelerated onset of cellular senescence in response to additional stresses.…”

Accumulation of Mitochondrial RPPH1 RNA Is Associated with Cellular Senescence

“…Senescence triggers dramatic changes in cellular physiology [ 33 ] including dramatic inhibition of transcription, RNA decay, and mRNA translation [ 34 , 35 ]. While the transcription rate is decreased dramatically, overall steady state levels of mRNAs do not change significantly during cellular senescence [ 36 ]. Recent studies revealed that senescence-associated secretory phenotype (SASP) is regulated by mTOR-mediated translation [ 37 , 38 ].…”