Elucidation to the anti tumor activity of KIF4A in uterine leiomyosarcoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16769
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Nakagawa Satoshi 大阪大学, 大学院医学系研究科, 助教 (30650593)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: leiomyosarcoma / LMS / KIF4A / antisense / biomarker

Outline of Final Research Achievements

We are currently analyzing the function of KIF4A, a molecule highly expressed in uterine leiomyosarcoma, which was identified using isobaric tags for relative and absolute quantitation (iTRAQ). We evaluated the cell proliferation rate of KIF4A knockdown cells by siren and found that proliferation was significantly suppressed (SK-LMS: -37.2±4.73%, SKN: -87.7±4.02%, SK-UT1- 28.1±3.00%, p<0.05). In vivo, down regulation of KIF4A with shRNA significantly suppressed tumor growth (SK-LMS:1186±4.02%, SK-UT1- 28.1±3.00%, p<0.05). (SK-LMS: 1186±118mm3 vs 461±84mm3, SK-UT1: 1704±441mm3 vs 514± 230mm3, p<0.05) Cell cycle analysis of the knockdown lines showed that the percentage of G2/M phase cells was significantly increased with KIF4A We also evaluated the expression of KIF4A in our clinical sample from 1999-2021, and found that 20/26 (77%) of the patients had KIF4A expression.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

治療法の確立されていない子宮平滑筋肉腫に対して、網羅的タンパクのスクリーニングを行った結果からKIF4Aを同定し、その機能解析を行った。子宮平滑筋肉腫は標準療法が確立されておらず、その治療戦略の１つとしての新規標的分子が腫瘍増殖に与える影響をin vitro, in vivoで証明したとともに、細胞周期がその機能に関与している可能性を明らかにした。本研究は、治療法の確立されていない平滑筋肉腫の治療についてKIF4Aが新規ターゲットの一つとなり得る点を証明したところが学術、社会的意義と考える。