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Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer.

Servín-González LS, Granados-López AJ, López JA - Int J Mol Sci (2015)

Bottom Line: Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling.In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer.Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de microRNAs, Unidad Académica de Ciencias Biológicas, Universidad Autónoma de Zacatecas, Av. Preparatoria S/N, Zacatecas 98066, Mexico. stevenservin07@gmail.com.

ABSTRACT
Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

No MeSH data available.


Related in: MedlinePlus

Regulation of AC-PKA-smac-caspase3 and PKC cell signaling by members of miR-181a-1~181b-1 and miR-181a-2~181b-2 clusters. Adenylyl cyclase (AC) induces PKA activation, generating CREB phosphorylation, which turns on smac/Diablo, causing caspase 3 activation. In addition, PKC activates caspase 3 and caspase 7. miR-181b, localized in clusters miR-181a-1~181b-1 and miR-181a-2~181b-2, downregulates AC; miR-181a also inhibits PKC protein expression. In bold are the miRNAs with effect on genes with validated experimental data.
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ijms-16-12773-f004: Regulation of AC-PKA-smac-caspase3 and PKC cell signaling by members of miR-181a-1~181b-1 and miR-181a-2~181b-2 clusters. Adenylyl cyclase (AC) induces PKA activation, generating CREB phosphorylation, which turns on smac/Diablo, causing caspase 3 activation. In addition, PKC activates caspase 3 and caspase 7. miR-181b, localized in clusters miR-181a-1~181b-1 and miR-181a-2~181b-2, downregulates AC; miR-181a also inhibits PKC protein expression. In bold are the miRNAs with effect on genes with validated experimental data.

Mentions: The miR-181 family is clustered on chromosomes 1, 9, and 19. MiR-181a-1 and miR-181b-1 are localized on chromosome 1, while miR-181a-2 and miR-181b-2 are on chromosome 9 and miR-181c and miR-181d are located on chromosome 19 [6]. Cluster miR-181a~181b presents advantages for cervical cancer development. It has been reported recently that miR-181a confers radiochemo-resistance by diminishing mRNA and proteins of PKC via 3′-UTR binding, therefore decreasing caspase 3/7 activity and hindering apoptosis [62,63] (Figure 4). miR-181b downregulates adenylyl cyclase (AC), restricting cAMP production and promoting cell proliferation and apoptosis diminution [64]. cAMP production is conducive to PKA activation, which induces transcription of smac/Diablo by CREB, which leads to caspase activation [65] (Figure 4). This pathway seems to be regulated by all members of the miR-181 family clustered on distinct chromosomes—In agreement with their similarity [66] and with in silico predictions (microRNA.org, MIRDB, and Target Scan).


Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer.

Servín-González LS, Granados-López AJ, López JA - Int J Mol Sci (2015)

Regulation of AC-PKA-smac-caspase3 and PKC cell signaling by members of miR-181a-1~181b-1 and miR-181a-2~181b-2 clusters. Adenylyl cyclase (AC) induces PKA activation, generating CREB phosphorylation, which turns on smac/Diablo, causing caspase 3 activation. In addition, PKC activates caspase 3 and caspase 7. miR-181b, localized in clusters miR-181a-1~181b-1 and miR-181a-2~181b-2, downregulates AC; miR-181a also inhibits PKC protein expression. In bold are the miRNAs with effect on genes with validated experimental data.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490472&req=5

ijms-16-12773-f004: Regulation of AC-PKA-smac-caspase3 and PKC cell signaling by members of miR-181a-1~181b-1 and miR-181a-2~181b-2 clusters. Adenylyl cyclase (AC) induces PKA activation, generating CREB phosphorylation, which turns on smac/Diablo, causing caspase 3 activation. In addition, PKC activates caspase 3 and caspase 7. miR-181b, localized in clusters miR-181a-1~181b-1 and miR-181a-2~181b-2, downregulates AC; miR-181a also inhibits PKC protein expression. In bold are the miRNAs with effect on genes with validated experimental data.
Mentions: The miR-181 family is clustered on chromosomes 1, 9, and 19. MiR-181a-1 and miR-181b-1 are localized on chromosome 1, while miR-181a-2 and miR-181b-2 are on chromosome 9 and miR-181c and miR-181d are located on chromosome 19 [6]. Cluster miR-181a~181b presents advantages for cervical cancer development. It has been reported recently that miR-181a confers radiochemo-resistance by diminishing mRNA and proteins of PKC via 3′-UTR binding, therefore decreasing caspase 3/7 activity and hindering apoptosis [62,63] (Figure 4). miR-181b downregulates adenylyl cyclase (AC), restricting cAMP production and promoting cell proliferation and apoptosis diminution [64]. cAMP production is conducive to PKA activation, which induces transcription of smac/Diablo by CREB, which leads to caspase activation [65] (Figure 4). This pathway seems to be regulated by all members of the miR-181 family clustered on distinct chromosomes—In agreement with their similarity [66] and with in silico predictions (microRNA.org, MIRDB, and Target Scan).

Bottom Line: Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling.In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer.Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio de microRNAs, Unidad Académica de Ciencias Biológicas, Universidad Autónoma de Zacatecas, Av. Preparatoria S/N, Zacatecas 98066, Mexico. stevenservin07@gmail.com.

ABSTRACT
Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

No MeSH data available.


Related in: MedlinePlus