miR-19a promotes colorectal cancer proliferation and migration by targeting TIA1.

Abstract

BACKGROUND:

Colorectal cancer (CRC) is a major worldwide health problem due to its high prevalence and mortality rate. T-cell intracellular antigen 1 (TIA1) is an important tumor suppressor involved in many aspects of carcinogenesis and cancer development. How TIA1 expression is regulated during CRC development remains to be carefully elucidated.

METHODS:

In CRC tissue sample pairs, TIA1 protein and mRNA levels were monitored by Western blot and qRT-PCR, respectively. Combining meta-analysis and miRNA target prediction software, we could predict microRNAs that targeted TIA1. Next, three CRC cell lines (SW480, Caco2 and HT29) were used to demonstrate the direct targeting of TIA1 by miR-19a. In addition, we investigated the biological effects of TIA1 inhibition by miR-19a both in vitro by CCK-8, EdU, Transwell, Ki67 immunofluorescence and Colony formation assays and in vivo by a xenograft mice model.

RESULTS:

In colorectal cancer (CRC), we found that TIA1 protein, but not its mRNA, was downregulated. We predicted that TIA1 was a target of miR-19a and validated that miR-19a binded directly to the 3'-UTR of TIA1 mRNA. miR-19a could promote cell proliferation and migration in CRC cells and accelerated tumor growth in xenograft mice by targeting TIA1.

CONCLUSIONS:

This study highlights an oncomiR role for miR-19a in regulating TIA1 in CRC and suggests that miR-19a may be a novel molecular therapeutic target for CRC.

• Authors: Yanqing Liu, Rui Liu, Fei Yang, Rongjie Cheng, Xiaorui Chen, Shufang Cui, Yuanyuan Gu, Wu Sun, Chaoying You, Zhijian Liu, Feng Sun, Yanbo Wang, Zheng Fu, Chao Ye, Chenyu Zhang, Jing Li, Xi Chen
• Journal: Molecular cancer (Mol Cancer) Vol. 16 Issue 1 Pg. 53 (03 04 2017) ISSN: 1476-4598 [Electronic] England
• PMID: 28257633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Apoptosis Regulatory Proteins
• MIRN19 microRNA, human
• MicroRNAs
• PDCD4 protein, human
• Poly(A)-Binding Proteins
• RNA, Messenger
• RNA-Binding Proteins
• T-Cell Intracellular Antigen-1
• TIA1 protein, human

Topics

• 3' Untranslated Regions
• Animals
• Apoptosis Regulatory Proteins (genetics)
• Binding Sites
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, myc
• Heterografts
• Humans
• Male
• Meta-Analysis as Topic
• Mice
• MicroRNAs (genetics)
• Poly(A)-Binding Proteins (genetics, metabolism)
• RNA Interference
• RNA Processing, Post-Transcriptional
• RNA, Messenger (genetics, metabolism)
• RNA-Binding Proteins (genetics)
• T-Cell Intracellular Antigen-1