Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene...Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene,has been found to regulate adipocyte development in an m^(6)A-dependent manner in multiple species.However,the effects of the m^(6)A methylation and FTO demethylation functions on chicken adipogenesis remain unclear.This study aims to explore the association between m^(6)A modification and chicken adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.Results:The association between m^(6)A modification and chicken lipogenesis was assessed by treating chicken pread-ipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine.The results showed that betaine significantly increased methylation levels and inhibited lipogenesis,and the inverse effect was found in preadipocytes after cycloleucine treatment.Overexpression of FTO significantly inhibited m^(6)A levels and promoted proliferation and differentiation of chicken preadipocytes.Silencing FTO showed opposite results.Mechanistically,FTO overexpression increased the expression of catenin beta 1(CTNNB1)by improving RNA stability in an m^(6)A-dependent manner,and we proved that FTO could directly target CTNNB1.Furthermore,CTNNB1 may be a positive regulator of adipogenesis in chicken preadipocytes.Conclusions:m^(6)A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes.FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.展开更多
Recent research has shown that the alteration of combinations in gene expression contributes to cellular phenotypic changes. Previously, it has been demonstrated that the combination of cadherin 1 and cadherin 2 expre...Recent research has shown that the alteration of combinations in gene expression contributes to cellular phenotypic changes. Previously, it has been demonstrated that the combination of cadherin 1 and cadherin 2 expression can identify the diffuse-type and intestinal-type gastric cancers. Although the diffuse-type gastric cancer has been resistant to treatment, the precise mechanism and phenotypic involvement has not been revealed. It may be possible that stem cells transform into gastric cancer cells, possibly through the involvement of a molecule alteration and signaling mechanism. In this review article, we focus on the role of catenin beta 1 (CTNNB1 or β-catenin) and describe the regulation of CTNNB1 signaling in gastric cancer and stem cells.展开更多
Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC...Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.展开更多
基金funded by the Natural Scientific Foundation of China(U1901206)Local Innovative and Research Teams Project of Guangdong Province(2019BT02N630)+4 种基金the Science and Technology Program of Guangdong province,China(2020B1212060060)the Science and Technology Program of Guangzhou,China(202103000084)the Construction Project of Modern Agricultural Science and Technology Innovation Alliance in Guangdong Province(2021KJ128)National Key R&D Program of China(2021YFD1300100)China Agriculture Research System(CARS-41-G03).
文摘Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene,has been found to regulate adipocyte development in an m^(6)A-dependent manner in multiple species.However,the effects of the m^(6)A methylation and FTO demethylation functions on chicken adipogenesis remain unclear.This study aims to explore the association between m^(6)A modification and chicken adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.Results:The association between m^(6)A modification and chicken lipogenesis was assessed by treating chicken pread-ipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine.The results showed that betaine significantly increased methylation levels and inhibited lipogenesis,and the inverse effect was found in preadipocytes after cycloleucine treatment.Overexpression of FTO significantly inhibited m^(6)A levels and promoted proliferation and differentiation of chicken preadipocytes.Silencing FTO showed opposite results.Mechanistically,FTO overexpression increased the expression of catenin beta 1(CTNNB1)by improving RNA stability in an m^(6)A-dependent manner,and we proved that FTO could directly target CTNNB1.Furthermore,CTNNB1 may be a positive regulator of adipogenesis in chicken preadipocytes.Conclusions:m^(6)A methylation of RNA was negatively associated with adipogenesis of chicken preadipocytes.FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.
文摘【目的】卵巢颗粒细胞的增殖和分化是原始卵泡生长启动的关键因素,卵巢颗粒细胞过度凋亡是卵泡闭锁的主要原因,因此卵巢颗粒细胞的功能对卵泡生长发育、排卵、激素分泌等至关重要。研究通过探究连环蛋白β1(catenin beta 1,CTNNB1)对猪卵泡发育过程中颗粒细胞的增殖、凋亡及类固醇激素分泌等功能的影响,为猪卵泡发育的分子调控机制研究提供参考。【方法】利用RNA抽提、实时定量PCR(Quantitative real time PCR,qRT-PCR)等方法,构建CTNNB1在母猪卵巢、肌肉、大脑等9个组织的表达谱;检测母猪性成熟过程中卵巢组织和小(≤3 mm)、中(3—6 mm)、大(≥6 mm)卵泡颗粒细胞中CTNNB1的表达情况。构建CTNNB1的真核表达载体及合成siRNA,转染至猪卵巢颗粒细胞,采用EdU、Annexin V-FITC/PI双染、ELISA等方法,检测CTNNB1对颗粒细胞增殖、凋亡、类固醇激素分泌的影响,以及对类固醇激素合成通路重要基因转录表达的影响。【结果】与肌肉、大脑等组织相比,CTNNB1在卵巢中mRNA表达水平最高。性成熟母猪卵巢中CTNNB1转录水平显著高于性成熟前和性成熟后的母猪;卵巢卵泡中CTNNB1转录和蛋白水平随卵泡发育明显上调;且卵巢颗粒细胞中CTNNB1转录和蛋白水平也随卵泡的发育逐渐上调。更重要的是,CTNNB1显著促进颗粒细胞增殖,抑制颗粒细胞凋亡;CTNNB1能够上调CYP1A1和HSD17B7的转录水平,下调CYP11A1、ESR1、ESR2、FSHR、LHR和NR5A1等类固醇激素合成相关基因的转录水平,进而促进颗粒细胞雌激素的分泌,抑制颗粒细胞雄激素和孕激素的分泌。【结论】本研究证实CTNNB1可能通过促进颗粒细胞增殖及雌激素的合成和分泌,抑制颗粒细胞凋亡及雄激素、孕激素的合成和分泌,进而促进卵泡的生长发育。
文摘Recent research has shown that the alteration of combinations in gene expression contributes to cellular phenotypic changes. Previously, it has been demonstrated that the combination of cadherin 1 and cadherin 2 expression can identify the diffuse-type and intestinal-type gastric cancers. Although the diffuse-type gastric cancer has been resistant to treatment, the precise mechanism and phenotypic involvement has not been revealed. It may be possible that stem cells transform into gastric cancer cells, possibly through the involvement of a molecule alteration and signaling mechanism. In this review article, we focus on the role of catenin beta 1 (CTNNB1 or β-catenin) and describe the regulation of CTNNB1 signaling in gastric cancer and stem cells.
基金supported by the Science and Technology Support Plan Key Projects of Tianjin(Grant No.20YFZCSY00070)the National Natural Science Foundation of China(Grant Nos.82073276,82273100)+1 种基金the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058)Science and Technology project of Health Commission of Tianjin Binhai New Area(Grant No.2022BWKY016).
文摘Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.
