Endometrial cancer （EC） is the most common and lethal gynaecological cancer type in Europe and in North America. Frequently EC arises more in the corpus proper and manifests as round, polypoid expansile masses, but ...Endometrial cancer （EC） is the most common and lethal gynaecological cancer type in Europe and in North America. Frequently EC arises more in the corpus proper and manifests as round, polypoid expansile masses, but it may also originate in the lower uterine segment or spread in endometrium with necrosis and hemorrhage. The analysis was performed using a custom panel containing all DNA sequences loci coding pre-miRNAs and genes related to biogenesis and regulation of sncRNAs in normal and tumor tissues extracted from 6 unrelated patients with endometrial carcinoma. The identified variations were correlated with mature miRNAs differentially expressed in the same normal and tumor endometrial tissues. The comparison analysis confirmed the high degree of cellular and genetic intratumoral heterogeneity with a temporal and spatial miRNA expression distribution in association with genomic variants identified. The classification of specific DNA mutations, onto the loci identified, should be suitable to characterize possible instability genome regions and help classification of tumors to ameliorate the clinical management of patients affected by endometrial carcinoma.展开更多
MicroRNAs（miRNAs） are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism ...MicroRNAs（miRNAs） are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English（including 6134 cases and 7141 controls） were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients（G allele vs A allele：OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%） and population-based studies（G allele vs A allele：OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%）.The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.展开更多
As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis....As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis.It was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to tumorigenesis.Here,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in AML.Moreover,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature miR-126.Mechanistically,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of pre-miR-126.YTHDF2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in AML.Overall,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.展开更多
The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated...The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3′ ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone m RNAs, m RNA fragments, U6 sn RNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area.展开更多
文摘Endometrial cancer （EC） is the most common and lethal gynaecological cancer type in Europe and in North America. Frequently EC arises more in the corpus proper and manifests as round, polypoid expansile masses, but it may also originate in the lower uterine segment or spread in endometrium with necrosis and hemorrhage. The analysis was performed using a custom panel containing all DNA sequences loci coding pre-miRNAs and genes related to biogenesis and regulation of sncRNAs in normal and tumor tissues extracted from 6 unrelated patients with endometrial carcinoma. The identified variations were correlated with mature miRNAs differentially expressed in the same normal and tumor endometrial tissues. The comparison analysis confirmed the high degree of cellular and genetic intratumoral heterogeneity with a temporal and spatial miRNA expression distribution in association with genomic variants identified. The classification of specific DNA mutations, onto the loci identified, should be suitable to characterize possible instability genome regions and help classification of tumors to ameliorate the clinical management of patients affected by endometrial carcinoma.
基金supported by China Natural Science Foundation (No.30901534)Jiangsu Province Natural Science Foundation(No. BK2009444)Grant for the 135 Key Medical Project of Jiangsu Province(No.XK201117)
文摘MicroRNAs（miRNAs） are gene regulators involved in numerous diseases including cancer,heart disease,neurological disorders,vascular abnormalities and autoimmune conditions.Although hsa-mir-499 rs3746444 polymorphism was shown to contribute to the susceptibility of multiple genes to cancer,the data have yielded conflicting results.Therefore,this meta-analysis was performed to provide a comprehensive assessment of potential association between hsa-mir-499 rs3746444 polymorphism and cancer risk.In this meta-analysis,a total of 9 articles regarding 10 eligible case-control studies in English（including 6134 cases and 7141 controls） were analyzed.No significant association between hsa-mir-499 rs3746444 polymorphism and overall cancer risk was demonstrated.However,an increased risk was observed in the subgroup of breast cancer patients（G allele vs A allele：OR = 1.10,95% CI = 1.00-1.20;P heterogeneity = 0.114;I 2 = 53.9%） and population-based studies（G allele vs A allele：OR = 1.12,95% CI = 1.00-1.25;P heterogeneity = 0.062;I 2 = 64.0%）.The findings suggested an association between hsa-mir-499 rs3746444 polymorphism and increased risk to breast cancer.
基金supported in part by the U.S.National Institutes of Health(NIH)grants R01 CA243386(J.C.),R01 CA271497,R01 CA214965(J.C.),R01 CA236399(J.C.),R01 DK124116(J.C)The Simms/Mann Family Foundation(J.C.).J.C.is a Leukemia&Lymphoma Society(LLS)Scholar and is supported by the LLS 2022 Scholar CDP Achievement Award.
文摘As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis.It was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to tumorigenesis.Here,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in AML.Moreover,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature miR-126.Mechanistically,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of pre-miR-126.YTHDF2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in AML.Overall,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.
基金supported by the National Institutes of Health(GM061146)National Science Foundation(IOS-1340001)the National Natural Science Foundation of China(91440105 and 31571332)
文摘The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3′ ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone m RNAs, m RNA fragments, U6 sn RNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area.
