Let-7c Inhibits NSCLC Cell Proliferation by Targeting HOXA1

Zhan, Min,Qu, Qiang,Wang, Guo,Liu, Ying-Zi,Tan, Sheng-Lan,Lou, Xiao-Ya,Yu, Jing,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

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.

공공 공유경제 플렛폼에서 LETS 활용에 관한 연구

이재민(LEE, Jae Min) 한국지역사회학회 2021 지역사회연구 Vol.29 No.4

공공 공유경제 플랫폼을 제공해 민간 공유경제를 활성화하려는 시도는 있었지만 커뮤니티 화폐 LETS를 내부 결제통화로 활용하려는 시도나 연구는 없었다. 본 연구에서는 공유경제 플랫폼과 LETS의 결합 효과를 살펴본다. 본 연구에서는 Acquier etl.(2019)가 분류한 공유 경제의 네 가지 비즈니스 모델을 활용한다. 플렛폼 내에서만 사용되는 LETS는 참가자들에게 공유경제의 이상적인 유형인 Commoners type이나 the mission-driven platforms type을 추구하게 만든다. 또한, LETS는 참가자들에게 이윤추구를 억제시키고, 이는 허구공유(Shared inflastruture providers type와 Matchmakers type)로 변질되는 경향을 억제한다는 것을 의미한다. 누구나 자유롭게 발행할 수 있는 LETS로 플렛폼에 일정 비율 의무적으로 남겨야 하는 가치는 공유부(CommonWealth)로 적립된다. LETS로 거래되는 플랫폼의 공유지(commons)는 신뢰이며, LETS 발행자가 부채를 상환하기 위해 플렛폼에 무언가를 제공할 때 신뢰가 유지된다. 그렇지 않고, LETS 발행자 각자가 자신의 이득만을 추구하여 플렛폼에 아무 것도 제공하지 않으면 거래가 단절되는 공유지의 비극이 일어난다. LETS시스템에서 거래계정은 모두에게 투명하게 공개된다. 따라서 참여자들의 계정을 개인들의 평판수단으로 활용하게 설계하면 공유지의 비극을 억제할 수 있다. 본래 LETS는 소규모 커뮤니티에서 잘 작동하기 때문에 설계에서는 Ostrom이 밝혀낸 공유지의 비극을 막았던 공동체의 8가지 기본설계원리에 따라 다층적 커뮤니티 네트워크설계방식을 고려해야 할 것이다. There have been some attempts to promote the private sector"s sharing economy by providing a public sharing economy platform, but there have been no attempts or studies to utilize the community currency LETS as an internal payment currency. This study looked at the effects of combining a sharing economy platform and LETS. This study utilizes the 4 types of the sharing economy business model of Acquier etl al. (2019). LETS makes participants to pursue the Commoners type or the mission-driven platforms type which seem ideal sharing economy types. In addition, LETS makes participants to weeken the pursuit of profit, which means to suppress pseudo-sharing(Shared inflastruture providers type and Matchmakers type). The value paid with LETS that anyone can freely issue, is reserved for CommonWealth. The commons of the LETS-traded platform is trust, and trust is maintained when the LETS issuer provides something to pay off debts. Otherwise, tragedy of the commons will occur. In LETS, trading accounts are open to all. Therefore designing the account as a reputation can curb the tragedy of the commons. Because LETS works well in small communities, a multi-layered community networks should be considered according to Otrom’s 8 design principals.

LET 증가에 따른 회복 생존 모델의 파라미터 값 비교

최은애(Eunae Choi) 한국방사선학회 2017 한국방사선학회 논문지 Vol.11 No.4

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/μm의 고LET 탄소빔 분할 조사 시 Potentially Lethal Damage Repair (PLDR)의 발생양을 확인하고 약 13keV/μm 저LET 조사와 비교하여 현저히 감소하였음을 확인하였다. PLDR의 감소에 따라 생존율 또한 감소하였다. 따라서 탄소빔의 생물리학적 모델 개발에 LET의 변화량은 반드시 고려되어져야 할 것으로 보 인다. Dose response curves using absorbed dose to the biological effect are usually available in case of conventional X beam. However, absorbed dose is not consider in treatment planning for carbon beam such as heavy ions. Because the biological effects also depend on other quantities such as the local variation, which is often characterized by the linear energy transfer (LET). So LQ model cannot explain the entire response of fractionated carbon beam irradiation. The variation in LET with penetration depth leads to substantial differences in biological effect of carbon beam. And it is therefore essential in treatment planning to calculate not only the absorbed dose but also the LET to estimate the biological outcome of the radiation of interest. LET variation plays an important role in the fractionated irradiations. It is suggested that consideration of LET is necessary in biophysical model.

Expression and Preliminary Functional Profiling of the let-7 Family during Porcine Ovary Follicle Atresia

Rui Cao,Wang Jun Wu,Xiao Long Zhou,Peng Xiao,Yi Wang,Honglin Liu 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.4

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.

Expression and Preliminary Functional Profiling of the let-7 Family during Porcine Ovary Follicle Atresia

Cao, Rui,Wu, Wang Jun,Zhou, Xiao Long,Xiao, Peng,Wang, Yi,Liu, Hong Lin Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.4

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.

Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70

Jiang, Tao,Wang, Xingang,Wu, Weiwei,Zhang, Fan,Wu, Shifeng Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.4

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.

Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

Juhyun Song,Mira Jun,Mok-Ryeon Ahn,Oh Yoen Kim 대한지역사회영양학회 2016 Nutrition Research and Practice Vol.10 No.4

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 μM) 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-α 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.

Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

Song, Juhyun,Jun, Mira,Ahn, Mok-Ryeon,Kim, Oh Yoen The Korean Nutrition Society 2016 Nutrition Research and Practice Vol.10 No.4

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.

마이스터 에크하르트의 그리스도교 신비주의

서동신(Dong-Shin, Seo) 한국종교학회 2013 宗敎硏究 Vol.73 No.-

This study is intended to show how Meister Eckhart understood spiritual problems of the nuns and Beguines who were in charge of pastoral care in Strassburg and Cologne in Germany in the early 14th century. He suggested that “Letting-go”(Abgeschiedenheit) should be the solution of “Selfishness”(Selbstischen Ich), the root of spiritual problems attaching to the created things and outer act, having a business oriented attitude, being satisfied with mental joy, and having the modes of will, intellect and possessions. The method used in this study is the exploration of historical context of ‘literal mediation’ in German works. <br/> Eckhart taking care of mainly the convent found a series of spiritual problems. He stated them partly not explicitly in the vernacular of German treatises and sermons. He continued the scholar intellect tradition of the Dominican order in engaging the place of life. While he searched for the solution of spiritual problems, he daringly had a new insight into letting-go, his own practice for nuns and Beguines. Letting-go which he made in German term is the way of letting-go all created things including the conception of reified God so that he can create something for himself. As long as love, humility and mercy are connected with things created, he emphasized to give priority to letting-go. Even if he stated in paradoxical literal presentation, such method was used in rhetoric of mystical documents. Letting go concerned with the solution of spiritual problems which can be sunned up in three aspects as follows: <br/> First, the precondition of letting-go is the unchangeable firm mind. It is like calm, divine and static sea different from love(contingent affection), hatred, sorrow, and even sufferings including the humility and mercy with the created things. <br/> Second, it makes human beings let-go things all created, to say, created things, him/herself and the concept of reified God and let him/her be identified in God`s grace. <br/> Third, it leads human beings to Purity, Simplicity, and Unchangeability that make human beings have the attributes of God. This meaning gives room to hermeneutic experiences in metaphysics. <br/> Therefore, Letting-go is a valuable approach in mystical practice as the solution of spiritual Selfishness from spiritual life in the early 14th century.

Let-7c miRNA Inhibits the Proliferation and Migration of Heat-Denatured Dermal Fibroblasts Through Down-Regulating HSP70

Shifeng Wu,Tao Jiang,Xingang Wang,Weiwei Wu,Fan Zhang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.4

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.