miR-29 and miR-30 regulate B-Myb expression during cellular senescence

Martínez, Iván; Cazalla, Demián; Almstead, Laura L.; Steitz, Joan A.; DiMaio, Daniel

doi:10.1073/pnas.1017346108

Cited by 192 publications

(172 citation statements)

References 33 publications

Supporting

Mentioning

160

Contrasting

Order By: Relevance

“…Furthermore, overexpression of miR-29 increased cell-cycle reentry in quiescent cells, whereas overexpression of let-7 and miR-125 delayed cell-cycle reentry (35). Modulation of miR-29 can also influence senescence, an irreversible growth-arrested state, by affecting B-myb expression (36). We also showed that during quiescence some miRNAs up-regulate the translation of their target mRNAs (37).…”

Section: Significancementioning

confidence: 66%

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

Martínez

Hayes

Barr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The reversible state of proliferative arrest known as "cellular quiescence" plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNAprocessing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduced expression of Exportin-5, a protein required for canonical miRNA biogenesis. The biogenesis of these quiescence-induced miRNAs is independent of Exportin-5 and depends instead on Exportin-1. Moreover, these quiescence-induced primary miRNAs (pri-miRNAs) are modified with a 2,2,7-trimethylguanosine (TMG)-cap, which is known to bind Exportin-1, and knockdown of Exportin-1 or trimethylguanosine synthase 1, responsible for (TMG)-capping, inhibits their biogenesis. Surprisingly, in quiescent cells Exportin-1-dependent pri-miR-34a is present in the cytoplasm together with a small isoform of Drosha, implying the existence of a different miRNA processing pathway in these cells. Our findings suggest that during quiescence the canonical miRNA biogenesis pathway is down-regulated and specific miRNAs are generated by an alternative pathway to regulate genes involved in cellular growth arrest.M ost metazoan cells enter a reversible cell-cycle arrest known as "cellular quiescence" when they are exposed to antimitogenic signals or an environment unfavorable for proliferation (1, 2). In mammalian cells, quiescence (also known as "G 0 arrest") is characterized by reduced DNA replication, altered metabolism, increased autophagy, and increased expression of cyclin-dependent kinase inhibitors such as p27 Kip1 (3,4). In vitro, quiescence can be induced in primary cells by serum starvation, contact inhibition, and loss of adhesion to a substrate (5). Quiescence is involved in important cellular processes, including the balance between differentiation and self-renewal in different types of stem cells, and dysregulation of quiescence could favor carcinogenesis. However, the molecular mechanisms that regulate quiescence are poorly understood (6). miRNAs are small, noncoding RNAs ∼22-nt long that regulate the expression of protein-coding genes by base-pairing with the 3′ UTR of mRNAs, repressing the translation and/or inducing the degradation of the target mRNA (7,8). In canonical miRNA biogenesis in mammalian cells, miRNAs are transcribed by RNA polymerase II to produce 7-methylguanosine (m 7 G)-capped primary miRNAs (pri-miRNAs) containing one or more bulged hairpin structures that are recognized by the nuclear microprocessor, which consists of the RNase III enzyme Drosha and the dsRNA-binding protein DGCR8 (DiGeorge syndrome critical region gene 8) (9-12). Specific cleavage of the pri-miRNA by the nuclear microprocessor generates an ∼70-nt stem-loop structure known as the "precursor miRNA" (pre-miRNA), which is recognized and transported to the cytoplasm by 10,11,13). Subsequently, pre-miRNA is cleaved by the cytoplasmic RNase III enzyme Dicer (14-17), generating a double-stranded mature mi...

show abstract

Section: Significancementioning

confidence: 66%

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

Martínez

Hayes

Barr

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…1b). miR-29 and miR-30 are implicated in senescence 27 and the DNA damage response, 28 indicating that CR regulates such essential processes through the miRNA response. miR-203 has been suggested to be an important tumor suppressor 29 and has been shown to affect the invasive potential of prostate cancer cell lines.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction

et al. 2012

View full text Add to dashboard Cite

Caloric restriction has been shown to increase lifespan in several organisms and to delay onset of age-related diseases. The transcriptional response to caloric restriction has been studied for mRnAs, while the microRnA signature following caloric restriction remains unexplored. here, we characterize the microRnA expression in mouse breast tissue before and after caloric restriction, reporting several changes in the microRnA expression profile. In particular, miR-203 is found to be highly induced by caloric restriction, and we demonstrate that caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric restriction. Using tissue culture models, we suggest that this regulation is important in both mouse and human. In conclusion, we show that the microRnA response induced by caloric restriction can regulate important factors in processes such as longevity and aging and is an integral and important component of the cellular response to caloric restriction.Caloric restriction (CR) has been shown to have a positive effect on life span across several organisms [1][2][3] and is speculated to be beneficial for the treatment of age-related diseases. Delineating the genetic response to CR is crucial to understand these effects on aging and disease and specifically in breast tissue since CR has been shown to have potential therapeutic benefit in diseases of the breast. 4,5

show abstract

“…The plethora of reports argue that microRNAs are master regulator of cancer biology, and deregulated expression of microRNAs affects all hallmarks of cancer [32] (Figure 2): (1) sustaining proliferative signaling (miR-21, let-7) [33,34]; (2) evading growth suppressors (miR-221 and miR-222) [35]; (3) resisting cell death (miR-34a, miR15a/16-1) [36,37]; (4) enabling replicative immortality (miR-29, miR-19b) [38,39]; (5) inducing angiogenesis (miR-210, miR-17-92 cluster) [40,41]; (6) activating invasion and metastasis (miR-10b, miR-224) [25,42]; (7) reprogramming energy metabolism (miR-23, miR-103) [43,44]; (8) evading immune destruction (miR-34a, miR-124a) [45,46].…”

Section: Micrornas and Human Cancermentioning

confidence: 99%

Non-coding RNAs: the cancer genome dark matter that matters!

Ling¹,

Girnita

Buda

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Protein-coding genes comprise only 3% of the human genome, while the genes that are transcribed into RNAs but do not code for proteins occupy majority of the genome. Once considered as biological darker matter, non-coding RNAs are now being recognized as critical regulators in cancer genome. Among the many types of non-coding RNAs, microRNAs approximately 20 nucleotides in length are best characterized and their mechanisms of action are well generalized. microRNA exerts oncogenic or tumor suppressor function by regulation of protein-coding genes via sequence complementarity. The expression of microRNA is aberrantly regulated in all cancer types, and both academia and biotech companies have been keenly pursuing the potential of microRNA as cancer biomarker for early detection, prognosis, and therapeutic response. The key involvement of microRNAs in cancer also prompted interest on exploration of therapeutic values of microRNAs as anticancer drugs and drug targets. MRX34, a liposome-formulated miRNA-34 mimic, developed by Mirna Therapeutics, becomes the first microRNA therapeutic entering clinical trial for the treatment of hepatocellular carcinoma, renal cell carcinoma, and melanoma. In this review, we presented a general overview of microRNAs in cancer biology, the potential of microRNAs as cancer biomarkers and therapeutic targets, and associated challenges.

show abstract

miR-29 and miR-30 regulate B-Myb expression during cellular senescence

Cited by 192 publications

References 33 publications

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence

MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction

Non-coding RNAs: the cancer genome dark matter that matters!

Contact Info

Product

Resources

About