• BMB Reports
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• v.53 no.12
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• pp.634-639
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• 2020

In prostate cancer, the androgen receptor (AR) transcription factor is a major regulator of cell proliferation and metastasis. To identify new AR regulators, we focused on Mixed lineage leukemia 5 (MLL5), a histone-regulating enzyme, because significantly higher MLL5 expression was detected in prostate cancer tissues than in matching normal tissues. When we expressed shRNAs targeting MLL5 gene in prostate cancer cell line, the growth rate and AR activity were reduced compared to those in control cells, and migration ability of the knockdown cells was reduced significantly. To determine the molecular mechanisms of MLL5 on AR activity, we proved that AR physically interacted with MLL5 and other co-factors, including SET-1 and HCF-1, using an immunoprecipitation method. The chromatin immunoprecipitation analysis showed reduced binding of MLL5, co-factors, and AR enzymes to AR target gene promoters in MLL5 shRNA-expressing cells. Histone H3K4 methylation on the AR target gene promoters was reduced, and H3K9 methylation at the same site was increased in MLL5 knockdown cells. Finally, xenograft tumor formation revealed that reduction of MLL5 in prostate cancer cells retarded tumor growth. Our results thus demonstrate the important role of MLL5 as a new epigenetic regulator of AR in prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4239-4242
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• 2013

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

• Journal of Applied Biological Chemistry
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• v.58 no.3
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• pp.219-226
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• 2015

The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.201-209
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• 2019

Mixed lineage leukemia proteins (MLL) are the key histone lysine methyltransferases that regulate expression of diverse genes. Aberrant activation of MLL promotes leukemia as well as solid tumors in humans, highlighting the urgent need for the development of an MLL inhibitor. We screened and isolated MLL1-binding ssRNAs using SELEX (${\underline{S}}ystemic$ ${\underline{E}}volution$ of ${\underline{L}}igands$ by ${\underline{E}}xponential$ enrichment) technology. When sequences in sub-libraries were obtained using next-generation sequencing (NGS), the most enriched aptamers-APT1 and APT2-represented about 30% and 26% of sub-library populations, respectively. Motif analysis of the top 50 sequences provided a highly conserved sequence: 5'-A[A/C][C/G][G/U][U/A]ACAGAGGG[U/A]GG[A/C] GAGUGGGU-3'. APT1, APT2, and APT5 embracing this motif generated secondary structures with similar topological characteristics. We found that APT1 and APT2 have a good binding activity and the analysis using mutated aptamer variants showed that the site information in the central region was critical for binding. In vitro enzyme activity assay showed that APT1 and APT2 had MLL1 inhibitory activity. Three-dimensional structure prediction of APT1-MLL1 complex indicates multiple weak interactions formed between MLL1 SET domain and APT1. Our study confirmed that NGS-assisted SELEX is an efficient tool for aptamer screening and that aptamers could be useful in diagnosis and treatment of MLL1-mediated diseases.

• Speech Sciences
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• v.8 no.3
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• pp.161-172
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• 2001

Ankyloglossia (tongue-tie) limits movement of the tongue connected with feeding and has adverse impacts on both dental health and speech. For the patients with ankyloglossia, surgical intervention is recommended as primary treatment. This study suggests the efficient tool in determining indicatory factors for frenulotomy by quantifying Maximum Lingual Length-Protrusion (MLL-P) with boley gauge, and as a preliminary study, to show the measurement results with normal children using the tool. The subjects were 61 normal children, and the distance (MLL-P) between mandibular central incisor and tongue tip during tongue protrusion was measured with a boley gauge (Digimatic $Caliper^{(R)}$). The results of this study can be summarized as follows: (1) The mean value of MLL-P (N=61 normal children) was 21.44 mm, (2) The mean value of MLL-P was 20.69 mm in males (N=33) and 21.91 mm in females (N=28). There was no statistically significant difference between males and females, (3) The mean value of MLL-P was 19.34 mm, 21.19 mm, 22.33 mm, 22.61 mm for measurement of 3-, 4-, 5- and 6-year-old children, respectively, and (4) The mean value of MLL-P showed statistically significant difference between 3- and 5-year-old children, between 3- and 6-year old children.

• The Korean Journal of Zoology
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• v.35 no.1
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• pp.29-36
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• 1992

The present study describes the production of monoclonal antibodies against cultured chick myoblast to pursue critical proteins in muscle cell fusion. Among a panel of monoclonal antibodies, three, Mll-3H 13, Mll-3Hl8 and Mll-3H35 were inhibited movblast fusion. A single 101-kDa antigen reactive with monoclonal antibody Mll-3H35 was detected by radioimmu-noprecipitation or by immunoblotting. During the course of myogenesis, the level of the protein remarkably decreased as the cells there differentiated. These results suggest that the protein platys a direct role in the process of myoblast fusion mechanism.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.48 no.3
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• pp.139-141
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• 2003

Disease severity, percent ripened grains, and yield were investigated in the seven mixtures by using near-isogenic lines having different resistant gene(s) to bacterial blight(BB) of rice. The seven mixtures including the four pure stands were inoculated with a 1:1:1 mixture of races $K_1$, $K_2$, and $K_3$ of BB. Among the seven mixtures-ML01, ML02, ML03, MLl2, MLl3, ML23 and ML0123-, disease severiety, percent ripened grains, and yield of ML01 and ML12, respectively did not show significant difference with those of mean values of their components. But degree of disease severity of the other mixtures, respectively -ML02, ML03, MLl3, ML23, and ML0123-was less than the mean of their components. Percent ripened grains and yield of them were higher than those of mean of their components. ML03, MLl3, ML23 and ML0123 comprised of the equal amount of two or four components having different resistant gene, these mixtures appeared to be a desirable combination for delaying spread of the pathogen, stabilizing of the race structure of the pathogen population, and extending durability of a cultivar with monogenic resistance.

• Journal of Trauma and Injury
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• v.36 no.3
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• pp.304-309
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• 2023

A Morel-Lavallée lesion (MLL) is a pathologic fluid collection within an abnormally formed space, resulting from an internal degloving injury between the muscle fascia and subcutaneous fat layer. Due to its resistance to conservative treatments such as drainage or compression dressing, various therapeutic methods have been developed for MLL. However, no standardized guidelines currently exist. Recently, endoscopic debridement and cutaneo-fascial suture (EDCS) has been introduced for the treatment of MLL, particularly for large lesions resistant to conservative approaches. While this procedure is known to be effective, limited reports are available on potential complications. The authors present a case of skin necrosis following EDCS for a massive MLL.

• Advances in Traditional Medicine
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• v.10 no.3
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• pp.150-154
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• 2010

The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.

• Molecules and Cells
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• v.41 no.5
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• pp.444-453
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• 2018

Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA-KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.