Nucleic Acids Res 2012,
PMID: 22210897
Zhu, Ying; Lu, Yang; Zhang, Qi; Liu, Jing-Jing; Li, Tuan-Jie; Yang, Jian-Rong; Zeng, Chunxian; Zhuang, Shi-Mei
The functional association between intronic miRNAs and their host genes is still largely unknown. We found that three gene loci, which produced miR-26a and miR-26b, were embedded within introns of genes coding for the proteins of carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family, including CTDSPL, CTDSP2 and CTDSP1. We conducted serum starvation-stimulation assays in primary fibroblasts and two-thirds partial-hepatectomies in mice, which revealed that miR-26a/b and CTDSP1/2/L were expressed concomitantly during the cell cycle process. Specifically, they were increased in quiescent cells and decreased during cell proliferation. Furthermore, both miR-26 and CTDSP family members were frequently downregulated in hepatocellular carcinoma (HCC) tissues. Gain- and loss-of-function studies showed that miR-26a/b and CTDSP1/2/L synergistically decreased the phosphorylated form of pRb (ppRb), and blocked G1/S-phase progression. Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb. Moreover, c-Myc, which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition. Our findings highlight the functional association of miR-26a/b and their host genes and provide new insight into the regulatory network of the G1/S-phase transition.
Diseases/Pathways annotated by Medline MESH: Neoplasms
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Text Mining Data
cyclin E1 ⊣ miR-26a/b: "
Further investigation disclosed that
miR-26a/b directly
suppressed the expression of CDK6 and
cyclin E1 , which resulted in reduced phosphorylation of pRb
"
CDK6 ⊣ miR-26a/b: "
Further investigation disclosed that miR-26a/b directly suppressed the expression of CDK6 and cyclin E1, which resulted in reduced phosphorylation of pRb
"
CTDSP ⊣ c-Myc: "
Moreover, c-Myc , which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition
"
miR-26 ⊣ c-Myc: "
Moreover, c-Myc , which is often upregulated in cancer cells, diminished the expression of both miR-26 and CTDSP family members, enhanced the ppRb level and promoted the G1/S-phase transition
"
Manually curated Databases
No curated data.