Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Yeom, Chul-gon; Kim, Dong-Il; Park, Min-jung; Choi, Joo-Hee; Jeong, Junkyeong; Wi, An-Jin; Whoa-Shig, Park; Han, Ho Jae; Park, Soo-Hyun

doi:10.1016/j.bbrc.2015.04.099

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…Based on CCK-8 and colony-forming assays, we found that the knockdown of CARM1 significantly reduced the OS cell proliferation. This result is similar to those of studies on hepatocytes 27 , lung cancer 28 , and colorectal cancer 29 , indicating that CARM1 may be an oncogene involved in proliferation and cell processes. The si-CARM1-treated OS cells exhibited a large S phase population.…”

Section: Discussionsupporting

confidence: 88%

The Overexpression of CARM1 Promotes Human Osteosarcoma Cell Proliferation through the pGSK3β/β-Catenin/cyclinD1 Signaling Pathway

Li¹,

Cheng²,

Zhu³

et al. 2017

Int. J. Biol. Sci.

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Osteosarcoma (OS) is a kind of malignant bone tumor that occurs frequently in the region surrounding the knee joint and poses a threat to the health of teenagers. Since the application of chemotherapy to treat OS, 5-year survival rate in patients has improved from 10% to 70%, but patient survival has not changed over the past four decades. Coactivator-associated arginine methyltransferase 1 (CARM1) is a member of the PRMT protein family; it acts as an oncogene in many cancers, but its function in OS is still unknown. In this study, we found that CARM1 is overexpressed in OS and its expression is correlated with the Enneking stage. CCK-8 and colony forming assays showed that proliferation in OS cell lines was downregulated when siRNA was used to knockdown CARM1 expression. The cell cycle was inhibited in S phase after si-CARM1 transfection in OS cell lines. An antibody array indicated that Erk1/2 (Thr202/Tyr204), PARS40 (Thr246), and GSK3β (Ser9) expression are affected by CARM1, and western blotting verified that CARM1 promotes OS cell proliferation via pGSK3β/β-catenin/cyclinD1 signaling. Accordingly, CARM1 is a crucial gene in OS and is a potential new treatment target.

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Section: Discussionsupporting

confidence: 88%

The Overexpression of CARM1 Promotes Human Osteosarcoma Cell Proliferation through the pGSK3β/β-Catenin/cyclinD1 Signaling Pathway

Li¹,

Cheng²,

Zhu³

et al. 2017

Int. J. Biol. Sci.

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“…Previous studies had clarified that PRMT4 expression was upregulated by high glucose levels in retinal pigment epithelial cells, 16 and by insulin in hepatocytes. 35 On the basis of our present analysis, we infer that the upregulation of PRMT4 in the adipose tissue of diabetic mice may be caused by hyperglycemia rather than insulin, the latter of which is deficient in diabetic mice. Since PRMT4 has been observed to be upregulated in the WAT of STZ-treated mice, what is the role of this enzyme plays in adipocyte function?…”

Section: Discussionmentioning

confidence: 58%

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

Peng

Zeng

et al. 2020

DMSO

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Purpose: Hypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4. Materials and Methods: Recombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis. Results: Elevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes. Conclusion: PRMT4 promotes lipolysis and increases serum triglyceride in T1DM.

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“…However, some mRNAs that acted as the alternative transcription of those circRNAs were found to participate in liver diseases. For instance, Cam1 is the linear transcript of circ_002319 and previous report showed that its up regulation facilitated hepatocyte proliferation [18]. Pvt1 is the linear transcript of circ_011235 and was found to promote proliferation and stem cell property of liver cancer [19].…”

Section: Discussionmentioning

confidence: 99%

CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis

et al. 2016

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The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as “miRNA sponge”. Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out. The overlapped predicted miRNAs as downstream targets of circRNAs and upstream regulators of mRNAs were verified by qRT-PCR and final circRNA-miRNA-mRNA network was constructed. Gene Ontology (GO) and KEGG pathway analysis were further applied to enrich the huge mRNA microarray data. To sum up, there were 69 up and 63 down regulated circRNAs as well as 2760 up and 2465 down regulated mRNAs in NASH group, comparing with control group. Randomly selected 13 of 14 mRNAs and 2 of 8 circRNAs were successfully verified by qRT-PCR. Through predicted overlapped miRNA verification, four circRNA-miRNA-mRNA pathways were constructed, including circRNA_002581-miR-122-Slc1a5, circRNA_002581- miR-122-Plp2, circRNA_002581-miR-122-Cpeb1 and circRNA_007585-miR-326- UCP2. GO and KEGG pathway analysis also enriched specific mRNAs. Therefore, circRNA profile may serve as candidate for NASH diagnosis and circRNA-miRNA -mRNA pathway may provide novel mechanism for NASH.

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Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation

Cited by 9 publications

References 23 publications

The Overexpression of CARM1 Promotes Human Osteosarcoma Cell Proliferation through the pGSK3β/β-Catenin/cyclinD1 Signaling Pathway

The Overexpression of CARM1 Promotes Human Osteosarcoma Cell Proliferation through the pGSK3β/β-Catenin/cyclinD1 Signaling Pathway

<p>Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice</p>

CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis

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