MiR-33 Contributes to the Regulation of Cholesterol Homeostasis

Rayner, Katey J.; Suárez, Yajaira; Dávalos, Alberto; Parathath, Saj; Fitzgerald, Michael L.; Tamehiro, Norimasa; Fisher, Edward A.; Moore, Kathryn J.; Fernández‐Hernando, Carlos

doi:10.1126/science.1189862

Cited by 1,114 publications

(1,216 citation statements)

References 17 publications

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“…These findings support our previous study that demonstrated that miR-223 targets SR-BI's 3′ UTR (41), and a recent study that reported that miR-223 regulates SR-BI in HepG2 cells (42). Hepatic miR-223 levels were found to be equal to or greater than other miRNAs that have been demonstrated to be physiologically relevant in the liver (18), and miR-223 inhibition was found to significantly increase SR-BI (SCARB1), HMGCS1, and SP3 mRNA levels, and significantly increase HDL-C uptake in Huh7 cells. In parallel to these direct effects, miR-223 was also found to have an indirect effect on cholesterol efflux because ABCA1 expression and function were found to be linked to intracellular miR-223 levels through the Sp3 TF.…”

Section: Discussionsupporting

confidence: 81%

“…In summary, we have described a small, but powerful regulator of metabolism because miR-223 likely coordinates cholesterol homeostasis through multiple direct and indirect mechanisms controlling cholesterol biosynthesis, uptake, and efflux. Results from this and other recent studies on miRNAs (13,18) highlight the potential importance of miRNAs in the etiology of dyslipidemias and cardiovascular disease. As such, miR-223 has great potential as a therapeutic target to control systemic cholesterol levels in the prevention and treatment of cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

“…Using a real-time PCR-based TaqMan array, we found that miR-223 was ranked no. 100 in primary human hepatocytes, greater than miR-33a (rank 250), miR-145 (rank 103), miR-221 (rank 124), and other functionally validated hepatic miRNAs (SI Appendix, Table S1) (18,20,21). In a recent study using small RNA sequencing to profile healthy "normal" human livers, miR-223 levels were reported to be greater than other previously validated miRNAs (22).…”

mentioning

confidence: 99%

“…Hepatic miR-223 levels were found to be significantly increased upon ischemic/reperfusion injury (16) and decreased in hepatocellular carcinoma (17). There is a growing list of miRNAs that have been reported to regulate individual mechanisms within cholesterol metabolism (18,19); however, miR-223 as a regulatory hub likely links multiple facets of the complex cholesterol metabolic network. In this study, we demonstrate that miR-223 transcription and mature levels are sensitive to intracellular cholesterol changes and that miR-223 regulates cholesterol biosynthesis, uptake, and efflux, thus establishing it as a critical posttranscriptional regulatory coordinator of cholesterol metabolism.…”

mentioning

confidence: 99%

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MicroRNA-223 coordinates cholesterol homeostasis

Vickers

Landstreet

Levin

et al. 2014

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

228

212

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Significance Results from this study represent a breakthrough in our understanding of posttranscriptional control of cholesterol metabolism and how microRNAs (miRNAs) are at the heart of cholesterol regulatory circuitry and homeostasis. Although cells are adept at maintaining proper cholesterol levels, it was unknown how cells posttranscriptionally coordinate cholesterol uptake, efflux, and synthesis. MicroRNA-223 (miR-223) transcription and expression are maintained by cholesterol, and, as a feedback network, miR-223 inhibits cholesterol biosynthesis and uptake and increases cholesterol efflux. This study clearly demonstrates the extensive role that miRNAs play in coordinating metabolic adaptation to disease and general homeostasis. This work highlights a unique regulatory control point for cholesterol homeostasis and illustrates how important the study of miRNAs is to the greater understanding of dyslipidemia and cardiovascular disease.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-223 coordinates cholesterol homeostasis

Vickers

Landstreet

Levin

et al. 2014

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

228

212

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“…While this manuscript was under revision, two independent laboratories reported similar findings (38,39).…”

Section: Methodsmentioning

confidence: 55%

miR-33 links SREBP-2 induction to repression of sterol transporters

Marquart

Allen

Ory

et al. 2010

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

505

501

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The sterol regulatory element binding protein 2 (SREBP-2) and the liver X receptor (LXR) control antagonistic transcriptional programs that stimulate cellular cholesterol uptake and synthesis, and cholesterol efflux, respectively. The clinical importance of SREBP-2 is revealed in patients with hypercholesterolemia treated with statins, which reduce low-density lipoprotein (LDL) cholesterol levels by increasing hepatic expression of SREBP-2 and its target, the LDL receptor. Here we show that miR-33 is encoded within SREBP-2 and that both mRNAs are coexpressed. We also identify sequences in the 3′ UTR of ABCA1 and ABCG1, sterol transporter genes both previously shown to be regulated by LXR, as targets for miR-33-mediated silencing. Our data show that LXR-dependent cholesterol efflux to both ApoAI and serum is ameliorated by miR-33 overexpression and, conversely, stimulated by miR-33 silencing. Finally, we show that ABCA1 mRNA and protein and plasma HDL levels decline after hepatic overexpression of miR-33, whereas they increase after hepatic miR-33 silencing. These results suggest novel ways to manage hypercholesterolemic patients.

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miR‐132 mediates a metabolic shift in prostate cancer cells by targeting Glut1

et al. 2016

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Prostate cancer is the second leading cause of cancer‐related deaths among men worldwide. Early diagnosis increases survival rates in patients but the survival rate has remained relatively poor over the past years. Increasing evidence shows that altered metabolism is a critical hallmark in prostate cancer. There is a strong need to explore the molecular mechanisms underlying cancer metabolism for prostate cancer therapy. Whether the aberrant expression of micro RNA (mi RNA ) contributes to cancer metabolism is not fully known. In this study, we found that micro RNA ‐132 (miR‐132) expression is reduced and thus leads to a metabolic switch in prostate cancer cells. miR‐132 performs this role by increasing Glut1 expression, resulting in the enhanced rate of lactate production and glucose uptake. The altered metabolism induced by decreased miR‐132 levels confers the rapid growth of the cancer cells. These data indicate that miR‐132 is involved in regulating the Warburg effect in prostate cancer by inhibiting Glut1 expression.

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MiR-33 Contributes to the Regulation of Cholesterol Homeostasis

Cited by 1,114 publications

References 17 publications

MicroRNA-223 coordinates cholesterol homeostasis

MicroRNA-223 coordinates cholesterol homeostasis

miR-33 links SREBP-2 induction to repression of sterol transporters

miR‐132 mediates a metabolic shift in prostate cancer cells by targeting Glut1

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