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Implications of miR cluster 143/145 as universal anti-oncomiRs and their dysregulation during tumorigenesis.

Das AV, Pillai RM - Cancer Cell Int. (2015)

Bottom Line: Tumorigenesis is a multistep process, de-regulated due to the imbalance of oncogenes as well as anti-oncogenes, resulting in disruption of tissue homeostasis.In many cases the effect of oncogenes and anti-oncogenes are mediated by various other molecules such as microRNAs. microRNAs are small non-coding RNAs established to post-transcriptionally regulate more than half of the protein coding genes. miR cluster 143/145 is one such cancer-related microRNA cluster which is down-regulated in most of the cancers and is able to hinder tumorigenesis by targeting tumor-associated genes.Their low levels precede events which lead to cancer progression and therefore could be considered also as biomarkers to stage the disease.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Program-9, Rajiv Gandhi Centre for Biotechnology, Thycaud.P.O., Thiruvananthapuram-14, Kerala India.

ABSTRACT
Tumorigenesis is a multistep process, de-regulated due to the imbalance of oncogenes as well as anti-oncogenes, resulting in disruption of tissue homeostasis. In many cases the effect of oncogenes and anti-oncogenes are mediated by various other molecules such as microRNAs. microRNAs are small non-coding RNAs established to post-transcriptionally regulate more than half of the protein coding genes. miR cluster 143/145 is one such cancer-related microRNA cluster which is down-regulated in most of the cancers and is able to hinder tumorigenesis by targeting tumor-associated genes. The fact that they could sensitize drug-resistant cancer cells by targeting multidrug resistant genes makes them potent tools to target cancer cells. Their low levels precede events which lead to cancer progression and therefore could be considered also as biomarkers to stage the disease. Interestingly, evidence suggests the existence of several in vivo mechanisms by which this cluster is differentially regulated at the molecular level to keep their levels low in cancer. In this review, we summarize the roles of miR cluster 143/145 in cancer, their potential prognostic applications and also their regulation during tumorigenesis.

No MeSH data available.


Related in: MedlinePlus

Schematic representing the involvement of miR cluster 143/145 in tumorigenesis. a Represents that some oncogenic signals can reduce the transcription of miR cluster 143/145 which in turn increase the tumorigenic events resulting in cancer. b On the other hand, anti-oncogenic signals can up-regulate this cluster which eventually can reduce tumorigenesis
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Fig2: Schematic representing the involvement of miR cluster 143/145 in tumorigenesis. a Represents that some oncogenic signals can reduce the transcription of miR cluster 143/145 which in turn increase the tumorigenic events resulting in cancer. b On the other hand, anti-oncogenic signals can up-regulate this cluster which eventually can reduce tumorigenesis

Mentions: The role of miR cluster 143/145 in cancer is of significance since both miR-143 and miR-145 have been shown to suppress tumorigenesis by targeting various genes that play significant roles during the development of cancer. Though these miRNAs have some common targets, they do have specific targets too, thus they act in concert or independently to impart the functions. On the other hand, miR cluster 143/145 is regulated, either positively or negatively, by various factors in cancer cells (Fig. 2). Evidence suggests that many oncogenes repress miR cluster 143/145 in order to impart their oncogenic effects in those cells, whereas anti-oncogenic factors, including transcription factors and drugs, elicit their effects through up-regulation of miR cluster 143/145. The mechanism of their regulation is different is different cell types. Both these miRNAs are supposed to be under the control of a common promoter, and are found to follow a similar pattern of expression in most of the cases. Since miR-145 has a specific upstream regulatory element of ~1.5 kb length, it could be possible that this miRNA is regulated independent of miR-143. This might be a possible reason for the disparity in the expression pattern of miR-145 and miR-143 in some cell types. However, the reason behind their differential regulation in different cell types is still unclear. More importantly, recent findings suggest that both the miRNAs play an important role in sensitizing cancer cells to various drugs which could be useful for formulating better combination therapy options for cancer. Moreover, expression levels of these miRNAs are most of the time reflected in the serum, suggesting their use as biomarkers for understanding prognosis of the disease. There have been few promising steps taken at the laboratory level to deliver these miRNAs efficiently to tumor sites and have to be investigated further. Taking all these evidences into consideration, miR cluster 143/145 can be regarded as ideal candidates for therapeutic interventions for cancers.Fig. 2


Implications of miR cluster 143/145 as universal anti-oncomiRs and their dysregulation during tumorigenesis.

Das AV, Pillai RM - Cancer Cell Int. (2015)

Schematic representing the involvement of miR cluster 143/145 in tumorigenesis. a Represents that some oncogenic signals can reduce the transcription of miR cluster 143/145 which in turn increase the tumorigenic events resulting in cancer. b On the other hand, anti-oncogenic signals can up-regulate this cluster which eventually can reduce tumorigenesis
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4588501&req=5

Fig2: Schematic representing the involvement of miR cluster 143/145 in tumorigenesis. a Represents that some oncogenic signals can reduce the transcription of miR cluster 143/145 which in turn increase the tumorigenic events resulting in cancer. b On the other hand, anti-oncogenic signals can up-regulate this cluster which eventually can reduce tumorigenesis
Mentions: The role of miR cluster 143/145 in cancer is of significance since both miR-143 and miR-145 have been shown to suppress tumorigenesis by targeting various genes that play significant roles during the development of cancer. Though these miRNAs have some common targets, they do have specific targets too, thus they act in concert or independently to impart the functions. On the other hand, miR cluster 143/145 is regulated, either positively or negatively, by various factors in cancer cells (Fig. 2). Evidence suggests that many oncogenes repress miR cluster 143/145 in order to impart their oncogenic effects in those cells, whereas anti-oncogenic factors, including transcription factors and drugs, elicit their effects through up-regulation of miR cluster 143/145. The mechanism of their regulation is different is different cell types. Both these miRNAs are supposed to be under the control of a common promoter, and are found to follow a similar pattern of expression in most of the cases. Since miR-145 has a specific upstream regulatory element of ~1.5 kb length, it could be possible that this miRNA is regulated independent of miR-143. This might be a possible reason for the disparity in the expression pattern of miR-145 and miR-143 in some cell types. However, the reason behind their differential regulation in different cell types is still unclear. More importantly, recent findings suggest that both the miRNAs play an important role in sensitizing cancer cells to various drugs which could be useful for formulating better combination therapy options for cancer. Moreover, expression levels of these miRNAs are most of the time reflected in the serum, suggesting their use as biomarkers for understanding prognosis of the disease. There have been few promising steps taken at the laboratory level to deliver these miRNAs efficiently to tumor sites and have to be investigated further. Taking all these evidences into consideration, miR cluster 143/145 can be regarded as ideal candidates for therapeutic interventions for cancers.Fig. 2

Bottom Line: Tumorigenesis is a multistep process, de-regulated due to the imbalance of oncogenes as well as anti-oncogenes, resulting in disruption of tissue homeostasis.In many cases the effect of oncogenes and anti-oncogenes are mediated by various other molecules such as microRNAs. microRNAs are small non-coding RNAs established to post-transcriptionally regulate more than half of the protein coding genes. miR cluster 143/145 is one such cancer-related microRNA cluster which is down-regulated in most of the cancers and is able to hinder tumorigenesis by targeting tumor-associated genes.Their low levels precede events which lead to cancer progression and therefore could be considered also as biomarkers to stage the disease.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Program-9, Rajiv Gandhi Centre for Biotechnology, Thycaud.P.O., Thiruvananthapuram-14, Kerala India.

ABSTRACT
Tumorigenesis is a multistep process, de-regulated due to the imbalance of oncogenes as well as anti-oncogenes, resulting in disruption of tissue homeostasis. In many cases the effect of oncogenes and anti-oncogenes are mediated by various other molecules such as microRNAs. microRNAs are small non-coding RNAs established to post-transcriptionally regulate more than half of the protein coding genes. miR cluster 143/145 is one such cancer-related microRNA cluster which is down-regulated in most of the cancers and is able to hinder tumorigenesis by targeting tumor-associated genes. The fact that they could sensitize drug-resistant cancer cells by targeting multidrug resistant genes makes them potent tools to target cancer cells. Their low levels precede events which lead to cancer progression and therefore could be considered also as biomarkers to stage the disease. Interestingly, evidence suggests the existence of several in vivo mechanisms by which this cluster is differentially regulated at the molecular level to keep their levels low in cancer. In this review, we summarize the roles of miR cluster 143/145 in cancer, their potential prognostic applications and also their regulation during tumorigenesis.

No MeSH data available.


Related in: MedlinePlus