• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• 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.

• Molecules and Cells
• /
• v.38 no.4
• /
• 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.

• BMB Reports
• /
• v.45 no.8
• /
• 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
• /
• v.10 no.4
• /
• 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.

• Communications of the Korean Mathematical Society
• /
• v.20 no.1
• /
• 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.

• Molecules and Cells
• /
• v.39 no.4
• /
• 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.

• Honam Mathematical Journal
• /
• v.39 no.2
• /
• pp.137-141
• /
• 2017

Let A be an abelian variety defined over a number field K and let L be a finite Galois extension of K. Let III(A/K) and III(A/L) denote, respectively, the Tate-Shafarevich groups of A over K and over L. Let $Res_{L/K}(A)$ be the restriction of scalars of A from L to K and let B be an abelian subvariety of $Res_{L/K}(A)$ defined over K. Assuming that III(A/L) is finite, we compute [III(B/K)][III(C/K)]/[III(A/L)], where [X] is the order of a finite abelian group X and the abelian variety C is defined by the exact sequence defined over K $0{\longrightarrow}B{\longrightarrow}Res_{L/K}(A){\longrightarrow}C{\longrightarrow}0$.

• Bulletin of the Korean Mathematical Society
• /
• v.49 no.6
• /
• pp.1303-1310
• /
• 2012

Let $p$ > 2 be a prime, and let $k{\geq}1$ be an integer. Let ${\chi}$ be a Dirichlet character modulo $p$, and let $L(s,{\chi})$ be the Dirichlet L-function corresponding to ${\chi}$. In this paper we consider the mean values of $$\sum_{{\chi}\;mod\;p\\{\chi}(-1)=-1}{\chi}(2^k)|L(1,\chi)|^2$$.

• Communications of the Korean Mathematical Society
• /
• v.20 no.4
• /
• pp.645-648
• /
• 2005

Let K be a Galois extension of a field F with G = Gal(K/F). Let L be an extension of F such that $K\;{\otimes}_F\;L\;=\; N_1\;{\oplus}N_2\;{\oplus}{\cdots}{\oplus}N_k$ with corresponding primitive idempotents $e_1,\;e_2,{\cdots},e_k$, where Ni's are fields. Then G acts on $\{e_1,\;e_2,{\cdots},e_k\}$ transitively and $Gal(N_1/K)\;{\cong}\;\{\sigma\;{\in}\;G\;/\;{\sigma}(e_1)\;=\;e_1\}$. And, let R be a commutative F-algebra, and let P be a prime ideal of R. Let T = $K\;{\otimes}_F\;R$, and suppose there are only finitely many prime ideals $Q_1,\;Q_2,{\cdots},Q_k$ of T with $Q_i\;{\cap}\;R\;=\;P$. Then G acts transitively on $\{Q_1,\;Q_2,{\cdots},Q_k\},\;and\;Gal(qf(T/Q_1)/qf(R/P))\;{\cong}\;\{\sigma{\in}\;G/\;{\sigma}-(Q_1)\;=\;Q_1\}$ where qf($T/Q_1$) is the quotient field of $T/Q_1$.

• Honam Mathematical Journal
• /
• v.32 no.1
• /
• pp.45-51
• /
• 2010

Let A be an abelian variety defined over a number field K and let L be a cyclic extension of K with Galois group G = <${\sigma}$> of order n. Let III(A/K) and III(A/L) denote, respectively, the Tate-Shafarevich groups of A over K and of A over L. Assume III(A/L) is finite. Let M(x) be a companion matrix of 1+x+${\cdots}$+$x^{n-1}$ and let $A^x$ be the twist of $A^{n-1}$ defined by $f^{-1}{\circ}f^{\sigma}$ = M(x) where $f:A^{n-1}{\rightarrow}A^x$ is an isomorphism defined over L. In this paper we compute [III(A/K)][III($A^x$/K)]/[III(A/L)] in terms of cohomology, where [X] is the order of an finite abelian group X.