MicroRNAs (miRNAs), which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene (miR-21) has been reported to be highly expressed in various s...MicroRNAs (miRNAs), which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene (miR-21) has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 (BMP-6) has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition (EMT) through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter (miPPR-21), we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3'UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.展开更多
Objective To explore the role and regulation of guanine nucleotide-binding protein G(i), a-1 subunit (GNAI1) in hepatocellular carcinoma (HCC). Methods Expression of GNAI1 in HCC samples was determined by qRT-PC...Objective To explore the role and regulation of guanine nucleotide-binding protein G(i), a-1 subunit (GNAI1) in hepatocellular carcinoma (HCC). Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.展开更多
Tomato has emerged as an emblematic model plants for fleshy fruit research and tomato fruit ripening is a complex and highly coordinated developmental process.The many physiology and biochemical processes associated w...Tomato has emerged as an emblematic model plants for fleshy fruit research and tomato fruit ripening is a complex and highly coordinated developmental process.The many physiology and biochemical processes associated with tomato fruit ripening require changes in the expression of hundreds to thousands of genes.Gene expression is regulated by transcriptional and post-transcriptional pathways,one of the recently discovered mechanisms in plants was small RNAs mediated gene silencing at post-transcriptional(PTGS) level.Intriguingly,several mi RNAs and endogenous si RNAs were revealed to be involved in the fruit ripening process which opened a new avenue in the field of fleshy fruit biology.This review compiled the most recent advances made in deciphering the regulation functions of mi RNAs and si RNAs in tomato fruit ripening.It also emphasized the new perspectives now possible in the small RNAs regulation research in tomato fruit ripening and senescence.展开更多
MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in post-transcriptional regulation. Their target genes are involved in a variety of biological processes such as development, metabolism, and ...MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in post-transcriptional regulation. Their target genes are involved in a variety of biological processes such as development, metabolism, and stress response. Panicum miliaceum L. (Panicum) is an important grain crop, but, until now, no miRNAs have been identified in this plant. Using a homology search based on expressed sequence tag (EST) analysis and miRNA precursor secondary structure, a total of 43 new miRNAs were identified. The miRNAs were found to be unevenly distributed among 11 miRNA families. Target analysis using the plant small RNA target analysis server psRNATarget showed that the newly identified miRNAs can potentially regulate 68 target genes. Ten of the 11 miRNA families were annotated as involved in RNA regulation, suggesting they may play an essential role in post-transcriptional regulation in Panicum. Selected miRNAs representing eight of the families were verified by northern blotting, indicating that the prediction method that we used to identify the miRNAs was effective.展开更多
HuR(ELAV11(embryonic lethal,abnormal vision)-like 1),a ubiquitously expressed member of the ELAV-like RNA-binding protein family,has been shown to regulate the stability and translation of mRNAs that encode factors re...HuR(ELAV11(embryonic lethal,abnormal vision)-like 1),a ubiquitously expressed member of the ELAV-like RNA-binding protein family,has been shown to regulate the stability and translation of mRNAs that encode factors regulating cellular senescence,thereby impacting on aging.In this review,we discuss the current knowledge of HuR’s role in vascular cell senescence and vascular aging.展开更多
文摘MicroRNAs (miRNAs), which are small noncoding RNA molecules, play important roles in the post-transcriptional regulation process. The microRNA-21 gene (miR-21) has been reported to be highly expressed in various solid tumors, including breast cancer. Bone morphogenetic protein-6 (BMP-6) has been identified as an inhibitor of breast cancer epithelial-mesenchymal transition (EMT) through rescuing E-cadherin expression. We initiated experi- ments to identify the relationships between miR-21 and BMP-6 in breast cancer progression. Real-time PCR analysis showed that miR-21 expression was very high in MDA-MB-231 cells that expressed little BMP-6. A reverse correla- tion between BMP-6 and miR-21 was also determined in breast cancer tissue samples. Moreover, BMP-6 inhibited miR-21 transcription in MDA-MB-231 cells. In order to investigate how BMP-6 inhibited the miR-21 promoter (miPPR-21), we constructed a series of miPPR-21 reporters. Luciferase assay results indicated that BMP-6 inhibited miPPR-21 activity through the E2-box and AP-l-binding sites. We also demonstrated that both δEF1 and TPA in- duced miR-21 expression. Using site-directed mutation and CHIP assay, we found that δEF1 induced miPPR-21 ac- tivity by binding to the E2-box on miPPR-21. Moreover, TPA triggered miPPR-21 activity through the AP-I binding sites. BMP-6 treatment significantly reduced the binding of these factors to miPPR-21 by decreasing the expression of δEF1 and c-Fos/c-Jun. We also demonstrated that BMP-6-induced downregulation of miR-21 modified the activ- ity of PDCD4 3'UTR and inhibited MDA-MB-231 cell invasion. δEF1 overexpression and TPA induction blocked this inhibitory effect of BMP-6. In conclusion, BMP-6-induced inhibition of miR-21 suggests that BMP-6 may function as an anti-metastasis factor by a mechanism involving transcriptional repression of miR-21 in breast cancer.
基金supported by grants from the National 973 Key Basic Research Program(No.2011CB933100)National Natural Science Foundation of China(No.81125016 and 81101481)+1 种基金Science and Technology Commission of Shanghai Municipality(No.11XD1404500 and 10JC1414200)Shanghai Health Bureau(No.XYQ2011047 and XBR2011039)
文摘Objective To explore the role and regulation of guanine nucleotide-binding protein G(i), a-1 subunit (GNAI1) in hepatocellular carcinoma (HCC). Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical (IHC) staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.
基金Supported by the National Natural Sciences Foundation of China(31401536)the Natural Science Foundation of Beijing(6144020)+1 种基金the Special Fund of China Agriculture Research System(CARS-25)the Special Fund for Agro-scientific Research in the Public Interest(201203095)
文摘Tomato has emerged as an emblematic model plants for fleshy fruit research and tomato fruit ripening is a complex and highly coordinated developmental process.The many physiology and biochemical processes associated with tomato fruit ripening require changes in the expression of hundreds to thousands of genes.Gene expression is regulated by transcriptional and post-transcriptional pathways,one of the recently discovered mechanisms in plants was small RNAs mediated gene silencing at post-transcriptional(PTGS) level.Intriguingly,several mi RNAs and endogenous si RNAs were revealed to be involved in the fruit ripening process which opened a new avenue in the field of fleshy fruit biology.This review compiled the most recent advances made in deciphering the regulation functions of mi RNAs and si RNAs in tomato fruit ripening.It also emphasized the new perspectives now possible in the small RNAs regulation research in tomato fruit ripening and senescence.
基金supported by the National Natural Science Foundation of China (Grant Nos. 30600384 and 50809068)the Young Outstanding Scholar Foundation of Northwest A & F University, China
文摘MicroRNAs (miRNAs) are a class of non-coding RNAs that play critical roles in post-transcriptional regulation. Their target genes are involved in a variety of biological processes such as development, metabolism, and stress response. Panicum miliaceum L. (Panicum) is an important grain crop, but, until now, no miRNAs have been identified in this plant. Using a homology search based on expressed sequence tag (EST) analysis and miRNA precursor secondary structure, a total of 43 new miRNAs were identified. The miRNAs were found to be unevenly distributed among 11 miRNA families. Target analysis using the plant small RNA target analysis server psRNATarget showed that the newly identified miRNAs can potentially regulate 68 target genes. Ten of the 11 miRNA families were annotated as involved in RNA regulation, suggesting they may play an essential role in post-transcriptional regulation in Panicum. Selected miRNAs representing eight of the families were verified by northern blotting, indicating that the prediction method that we used to identify the miRNAs was effective.
基金supported by the National Natural Science Foundation of China(81230008,91339114)111 project of Ministry of Education of China(B07001)
文摘HuR(ELAV11(embryonic lethal,abnormal vision)-like 1),a ubiquitously expressed member of the ELAV-like RNA-binding protein family,has been shown to regulate the stability and translation of mRNAs that encode factors regulating cellular senescence,thereby impacting on aging.In this review,we discuss the current knowledge of HuR’s role in vascular cell senescence and vascular aging.