Wednesday, July 6, 2022

This regulatory RNA molecule help block a cancer-promoting gene expression

MiR-766-5p-mediated control of CBP and BRD4 blocks the formation of super-enhancers.

Cancer is triggered by abnormal and uncontrolled gene expression. Various molecular mechanisms play a vital role inactivation and overexpression of oncogenes in cancer.

Recently, scientists from the Tokyo Medical and Dental University (TMDU) have found a small RNA molecule called a microRNA (miRNA or miR) that can help block the expression of a powerful cancer-promoting gene. In research, it was found that the molecule called miR-766-5preduces expression of oncogene MYC, a critical cancer-promoting gene.

MiRNAs can directly bind and interact with specific gene messages and block them from translating into a protein. Hence, any molecular pathway controlled by that particular protein is also affected by this miRNA-mediated regulation.

A past study in which miR-766-5p was used to treating cancer cells demonstrated lower MYC expression. It also inhibited cancer cell growth rates.

What is the specific mechanism behind these results? This study, which sought to determine the mechanism, found that miR-766-5p could directly target and reduce the expression of two proteins called CBP and BRD4.

CBP can induce a molecular change called acetylation that causes DNA to become more “open,” which allows genes present in that area to be more easily expressed. BRD4 can then be recruited to these sites and help promote transcription of these gene messages.

Johji Inazawa, a senior author, said, “Areas of DNA with high activity of proteins like CBP and BRD4 are known as super-enhancers. Many cancer cells develop super-enhancers near oncogenes, like MYC, that drive increased oncogene expression and therefore promote cancer.”

During experiments, scientists treated the cells with a synthetic version of miR-766-5p. The MYC levels were decreased in cancer cells due to the suppression of CBP and BRD4. Also, tumors engrafted in lab mice showed significantly suppressed growth when treated with miR-766-5p compared with a control miRNA.

Lead author of the study Yasuyuki Gen said“Our findings suggest that miR-766-5p-mediated control of CBP and BRD4 blocks formation of the super-enhancers that contribute to MYC overexpression in cancer cells.”

Journal Reference:
  1. Yasuyuki Gen, Tomoki Muramatsu, Jun Inoue, Johji Inazawa. miR-766-5p targets super-enhancers by downregulating CBP and BRD4. Cancer Research, 2021; canres.0649.2021 DOI: 10.1158/0008-5472.CAN-21-0649

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