MiR-29a, targeting caveolin 2 expression, is responsible for limitation of pancreatic cancer metastasis in patients with normal level of serum CA125.
Chen LiangSi ShiQingcai MengDingkong LiangJie HuaYi QinBo ZhangJin XuQuanxing NiXian-Jun YuPublished in: International journal of cancer (2018)
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal tumors, with an overall 5-year survival rate less than 8%. The dismal prognosis is mainly due to aggressive potential for metastasis. Hence, there is an urgent need for a better understanding of the molecular mechanisms underlying pancreatic cancer invasion and metastasis to improve the unfavorable overall survival (OS) of PDAC patients. In this study, we identified microRNA-29a (miR-29a) as an important tumor suppressor, which was downregulated in PDAC tissues. Moreover, miR-29a counteracted MUC16-mediated migration and invasion. In the pancreatic cancer cells, MUC16 upregulated c-Myc expression, which enhanced c-Myc binding to E-box in the miR-29a promoter and inhibited miR-29a transcription. Thus, miR-29a was negatively correlated with both MUC16 expression and serum CA125 levels. Furthermore, caveolin 2 (CAV2) was demonstrated to be the target of miR-29a by bioinformatics and luciferase reporter assays, and high CAV2 expression was responsible for a poor prognosis, especially in the subgroup with normal CA125 levels. Thus, the present study explains why high levels of serum CA125 are correlated with PDAC metastasis, highlighting the predictive value of this marker in PDAC patients.
Keyphrases
- poor prognosis
- long non coding rna
- cell proliferation
- long noncoding rna
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- gene expression
- peritoneal dialysis
- transcription factor
- dna methylation
- randomized controlled trial
- prognostic factors
- clinical trial
- binding protein
- risk assessment
- crispr cas
- patient reported outcomes
- study protocol
- single cell
- free survival
- patient reported
- cell migration
- double blind