JOURNAL ARTICLE

MicroRNA-449a functions as a tumor suppressor in pancreatic cancer by the epigenetic regulation of ATDC expression

Feng Li, Jing Liang, Lu Bai
Biomedicine & Pharmacotherapy 2018, 103: 782-789
29684857
A growing body of evidence has suggested that microRNAs (miRNAs) play a pivotal role in the development and progression of pancreatic cancer. miRNA-449a (miR-449a) has attracted particular interest due to its critical role in regulating cancer biology in numerous cancer types. However, whether miR-449a is involved in the regulation of pancreatic cancer development and progression remains unknown. In this study, we aimed to investigate the expression pattern and potential biological function of miR-449a in pancreatic cancer. Our results showed that miR-449a levels were significantly down-regulated in pancreatic cancer tissues and cell lines. The overexpression of miR-449a significantly inhibited the proliferation and invasion of pancreatic cancer cells, whereas miR-449a inhibition promoted the proliferation and invasion of pancreatic cancer cells. Bioinformatic analysis predicted that ataxia-telangiectasia group D complementing gene (ATDC) was a potential target gene of miR-449a. The dual-luciferase reporter assay revealed that miR-449a directly binds to the 3'-untranslated region of ATDC. Further analysis demonstrated that miR-449a negatively controls the mRNA and protein expression of ATDC in pancreatic cancer cells. In addition, an inverse correlation between miR-449a and ATDC expression was observed in clinical tissues. Notably, the overexpression of ATDC partially reversed the antitumor effect of miR-449a overexpression, while the silencing of ATDC abrogated the oncogenic effect of miR-449a inhibition in pancreatic cancer cells. In addition, the overexpression of miR-449a inhibited the accumulation of β-catenin and blocked the activation of Wnt signaling by targeting ATDC. Taken together, our study reveals a tumor suppressive role of miR-449a in pancreatic cancer, and demonstrates that the antitumor role of miR-449a is associated with its regulatory effect on ATDC expression. Our study suggests that the miR-449a/ATDC axis may play an important role in the development and progression of pancreatic cancer and may provide potential targets for the development of cancer therapies.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
29684857
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"