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miR-199a
miR-199a is a short non-coding RNA, encoded by two loci in the human genome: miR-199a-1 on Chromosome 19, and miR-199a-2 on Chromosome 1. miR-199 has two mature forms: miR-199a-3P and miR-199a-5P, which are generated from both strands of pre-miR-199a. It was noticed that the transcription of miR-199a-2 and miR-214 is controlled by the same promoter (miR-199a-2). Furthermore, co-expression of miR-199a and miR-214 is found in many diseases. Besides, epigenetics changes such as DNA methylation and histone modification can decrease the miR-199a expression. And TWSIT1 and EGR1 activation increase the expression of miR-199a by binding to the promoter of miR-199a-2 on Chromosome1.
Functions of miR-199a
The functions of miR-199a are complex in different conditions. It was demonstrated that under hypoxic conditions, miR-199a is rapidly down-regulated to protect cardiomyocyte. During liver and lung tissue fibrosis, miR-199a is increased and is thought to be a major regulator. In respect of cancers, the roles of miR-199a seem to be more complicated. For example, miR-199a is elevated in gastric cancer or metastatic tissues, as well as in colorectal cancer and adenocarcinoma. High expression of miR-199a may predict a poor prognosis. However, it is downregulated in liver cancer, ovarian cancer, bladder cancer, suggesting that it may act as tumor suppressor during the cancer progression. In liver cancer, it targets mTOR, PAK4 and CD44 to function as tumor suppressor. And, it was shown that miR-199a is associated with tumor progression and chemoresistance in ovarian cancer by regulating IKKβ expression.
Fig. 1 Summary of key factors relating to miR-199a and its functions on different targets. (Shen, G., 2012)
miR-199a for Cholangiocarcinoma Diagnosis
Considering its powerful role in tumorigenesis, many studies have investigated the role of miR-199a in cholangiocarcinoma. Accordingly, it is downregulated in cholangiocarcinoma. Recently, it has been illustrated that mTOR is a target of miR-199a. Overexpression of miR-199a in cholangiocarcinoma cells induces inhibition of mTOR and p-mTOR by binding to the mTOR gene and subsequently regulating 4E-BP1 and P70SK6 phosphorylation. Thus, it is indicated that miR-199a plays an important role in inhibition of mTOR in cholangiocarcinoma. It is considered to be a promising biomarker for the diagnosis and prognosis of patients with cholangiocarcinoma.
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Reference
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