Investigation of potential therapeutic targets for esophageal squamous cell carcinoma focused on the functional modification of cancer stimulating RNA binding protein.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokushima
• Principal Investigator: MASUDA Kiyoshi 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (00457318)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: RNA結合蛋白質 / 転写後調節機構 / 食道がん

Outline of Final Research Achievements

We found two RBPs, TIA1 and KHSRP, could have tumor-promoting functions in esophagus cancer.
Among two major isoforms of human TIA1, TIA1a and TIA1b, TIA1a was expressed in both the nucleus and cytoplasm. We revealed that only TIA1a promoted anchorage-dependent and anchorage-independent cell proliferation via induction of cell cycle promoters, such as CCNA2 and SKP2. Then, we found that phosphorylation of the specific amino acid residue within TIA1a could regulate molecular function of TIA1a and introduced synthetic peptide could efficiently translocate cytoplasmic TIA1a into nuclear.
We also found that KHSRP silencing inhibited cell growth, and migration/invasion in ESCC cells. miRNA microarray analysis identified a set of KHSRP-regulating miRNAs, including miR-150b, miR-21, and miR-301a. Silencing of KHSRP reduced expressions of these miRNAs and suppressed migration/invasion of ESCC cells with higher levels of their target mRNAs and proteins, including BMP6, TIMP3 and PDCD4.

Free Research Field

RNA生物学