MiR‐29a, targeting caveolin 2 expression, is responsible for limitation of pancreatic cancer metastasis in patients with normal level of serum CA125. Issue 11 (29th September 2018)

• Record Type: Journal Article
• Authors: Liang, Chen; Shi, Si; Meng, Qingcai; Liang, Dingkong; Hua, Jie; Qin, Yi; Zhang, Bo; Xu, Jin; Ni, Quanxing; Yu, Xianjun
• Is Part Of: International journal of cancer. Volume 143:Issue 11(2018)
• Page Start: 2919
• Page End: 2931
• Publication Date: 2018-09-29
• Subjects: MUC16/CA125 -- miR‐29a -- pancreatic cancer -- metastasis -- caveolin 2; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31654
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : 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. Abstract : What's new? Cancer antigen 125 (CA125), a peptide epitope of mucin 16, is known as a biomarker of ovarian and pancreatic cancer. Here the authors uncover a suppressive role of a single microRNA, miR‐29a, in mucin 16‐mediated cell migration and invasion and show miR‐29a levels to be negatively correlated with CA125 levels in pancreatic ductal adenocarcinoma. Moreover, miR‐291‐mediated downregulation of caveolin 2, an oncogene usually overexpressed in pancreatic cancers, was significantly associated with a better clinical prognosis, especially in patients with normal CA125 levels, highlighting the potential predictive value of miR‐29a in pancreatic cancer.