• Asian Pacific Journal of Cancer Prevention
• /
• 제14권1호
• /
• pp.387-392
• /
• 2013

Objective: The aim of the present study was to explore mechanisms by which let-7c suppresses NSCLC cell proliferation. Methods: The expression level of let-7c was quantified by qRT-PCR. A549 and H1299 cells were transfected with let-7c mimics to restore the expression of let-7c. The effects of let-7c were then assessed by cell proliferation, colony formation and cell cycle assay. Mouse experiments were used to confirm the effect of let-7c on tumorigenicity in vivo. Luciferase reporter assays and Western blotting were performed to identify target genes for let-7c. Results: HOXA1 was identified as a novel target of let-7c. MTS, colony formation and flow cytometry assays demonstrated that forced expression of let-7c inhibited NSCLC cell proliferation by inducing G1 arrest in vitro, consistent with inhibitory effects induced by knockdown of HOXA1. Mouse experiments demonstrated that let-7c expression suppressed tumorigenesis. Furthermore, we found that let-7c could regulate the expression of HOXA1 downstream effectors CCND1, CDC25A and CDK2. Conclusions: Collectively, these results demonstrate let-7c inhibits NSCLC cell proliferation and tumorigenesis by partial direct targeting of the HOXA1 pathway, which suggests that restoration of let-7c expression may thus offer a potential therapeutic intervention strategy for NSCLC.

• 비교문화연구
• /
• 제27권
• /
• pp.387-414
• /
• 2012

This paper is intended to describe the idiosyncratic aspects of the 'let alone' construction in English, clarifying the productivity property of this construction and to show that this construction displays the properties of prepositional phrase that denote the meaning of 'the comparison of degree', against the claim that this construction should be regarded as a coordinating conjunction. In the process of doing that, this paper classifies this 'let alone' construction into two types of construction, by investigating the external and internal syntactic distributions of 'let alone' constructions as well as the relationship between 'let alone' phrases and the main clause.

• Molecules and Cells
• /
• 제38권4호
• /
• pp.304-311
• /
• 2015

Most follicles in the mammalian ovary undergo atresia. Granulosa cell apoptosis is a hallmark of follicle atresia. Our previous study using a microRNA (miRNA) microarray showed that the let-7 microRNA family was differentially expressed during follicular atresia. However, whether the let-7 miRNA family members are related to porcine (Sus scrofa) ovary follicular apoptosis is unclear. In the current study, real-time quantitative polymerase chain reaction showed that the expression levels of let-7 family members in follicles and granulosa cells were similar to our microarray data, in which miRNAs let-7a, let-7b, let-7c, and let-7i were significantly decreased in early atretic and progressively atretic porcine ovary follicles compared with healthy follicles, while let-7g was highly expressed during follicle atresia. Furthermore, flow cytometric analysis and Hoechst33342 staining demonstrated that let-7g increased the apoptotic rate of cultured granulosa cells. In addition, let-7 target genes were predicted and annotated by TargetScan, PicTar, gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our data provide new insight into the association between the let-7 miRNA family in granulosa cell programmed death.

• 대한수학회논문집
• /
• 제9권4호
• /
• pp.783-796
• /
• 1994

Let V be a vector space of dimension m over Q, and let (, ) be a non-degenerate bilinear form on V. Let r be the Witt index of V, and let $V = V' + V_0 + V"$ be the Witt decomposition, where $V_0$ is anisotropic and V', V" are paired non-singularly. Let H = O(m-r, r) be the isometry group of V, (, ), viewed as an algebraic group over Q. Let G = Sp(n) be the symplectic group of rank n defined over Q.ed over Q.

• BMB Reports
• /
• 제45권8호
• /
• pp.464-469
• /
• 2012

Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play a critical role in atherosclerosis. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. MiRNA let-7 family is known to be involved in the regulation of cell apoptosis. However, the function of let-7 in ox-LDL induced ECs apoptosis and atherosclerosis is still unknown. Here, we show that let-7c expression was markedly up-regulated in ox-LDL induced apoptotic human umbilical cord vein endothelial cells (HUVECs). Let-7c over-expression enhanced apoptosis in ECs whereas inhibition of let-7c could partly alleviate apoptotic cell death mediated by ox-LDL. Searching for how let-7c affected apoptosis, we discovered that antiapoptotic protein Bcl-xl was a direct target of let-7c in ECs. Our data suggest that let-7c contributes to endothelial apoptosis through suppression of Bcl-xl.

• Nutrition Research and Practice
• /
• 제10권4호
• /
• pp.377-384
• /
• 2016

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

• 한국방사선학회논문지
• /
• 제11권4호
• /
• pp.177-181
• /
• 2017

방사선 생물학적 효과(Radio biological effectiveness, RBE)를 선량에 대부분 의존하는 X선과 달리 탄소빔의 경우 LET의 변화량은 반드시 고려되어야할 사항이다. 이는 X선 과는 극히 대조적인 선량 분포도를 갖고 있기 때문이며 LET의 변화량이 중요한 이유가 된다. 따라서 기존의 LQ 모델이나 회복생존모델의 경우 이러한 점이 감안되지 않아 탄소빔의 분할 조사 시 문제점을 보이며 오류를 보이고 있다. 본 연구에서는 약 $75keV/{\mu}m$의 고LET 탄소빔 분할 조사 시 Potentially Lethal Damage Repair (PLDR)의 발생양을 확인하고 약 $13keV/{\mu}m$ 저LET 조사와 비교하여 현저히 감소하였음을 확인하였다. PLDR의 감소에 따라 생존율 또한 감소하였다. 따라서 탄소빔의 생물리학적 모델 개발에 LET의 변화량은 반드시 고려되어져야 할 것으로 보인다.

• 대한수학회논문집
• /
• 제20권1호
• /
• pp.23-34
• /
• 2005

Let R be a ring with left identity. Let G : $R{\times}R{\to}R$ be a symmetric biadditive mapping and g the trace of G. Let ${\alpha}\;:\;R{\to}R$ be an endomorphism and ${\beta}\;:\;R{\to}R$ an epimorphism. In this paper we show the following: (i) Let R be 2-torsion-free. If g is (${\alpha},{\beta}$)-skew-commuting on R, then we have G = 0. (ii) If g is (${\beta},{\beta}$)-skew-centralizing on R, then g is (${\beta},{\beta}$)-commuting on R. (iii) Let $n{\ge}2$. Let R be (n+1)!-torsion-free. If g is n-(${\alpha},{\beta}$)-skew-commuting on R, then we have G = 0. (iv) Let R be 6-torsion-free. If g is 2-(${\alpha},{\beta}$)-commuting on R, then g is (${\alpha},{\beta}$)-commuting on R.

• 디지털콘텐츠
• /
• 11호통권114호
• /
• pp.90-91
• /
• 2002

KT가 민영 KT의 역점사업으로 인터넷 서비스 사업자들을 위한 'Let's KT' 사업을 본격적으로 추진하면서 업계의 관심을 끌고 있다. KT의 이번 Let's KT 사업은 포탈사업자, 콘텐츠사업자, 솔루션사업자 등을 대상으로 가입자 관리와 인증, 결제 과정을 KT의 Let's KT 홈페이지를 통해 별도의 가입절차 없이 한번의 로그인으로 손쉽게 이용할 수 있도록 지원하는 것이 골자다. 업계에서는 KT가 '새로운 KT만들기'의 일환으로 Let's KT 사업을 통해 국내 인터넷 비즈니스의 구심점으로 나서고자 하고 있으며 이를 통해 새롭게 KT의 위상을 확립하려 하는 것으로 평가하고 있다.

• Molecules and Cells
• /
• 제39권4호
• /
• pp.345-351
• /
• 2016

Wound healing is a complex physiological process necessitating the coordinated action of various cell types, signals and microRNAs (miRNAs). However, little is known regarding the role of miRNAs in mediating this process. In the present study, we show that let-7c miRNA is decreased in heat-denatured fibroblasts and that inhibiting let-7c expression leads to the increased proliferation and migration of dermal fibroblasts, whereas the overexpression of let-7c exerts an opposite effect. Further investigation has identified heat shock protein 70 as a direct target of let-7c and has demonstrated that the expression of HSP70 in fibroblasts is negatively correlated with let-7c levels. Moreover, down-regulation of let-7c expression is accompanied by up-regulation of Bcl-2 expression and down-regulation of Bax expression, both of which are the downstream genes of HSP70. Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. Overall, we have identified let-7c as a key regulator that inhibits fibroblasts proliferation and migration during wound healing.