Alteration of cancer cell traits by hnRNP A1 loss and subsequent ncRNA release during starvation.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Musashino University
• Principal Investigator: Takahashi Tetsuyuki 武蔵野大学, 薬学部, 講師 (00403692)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: hnRNP A1 / 栄養飢餓状態 / ノンコーディングRNA

Outline of Final Research Achievements

The study achieved the following three results.
1. The starvation-induced hnRNP A1 protein loss was due to the miR-4745-5p and miR-6798-5p-mediated translational repression. 2. CCND1 mRNA, a novel hnRNP A1-binding mRNA, was destabilized by starvation, and this destabilization was defined by the RRM1 domain within the hnRNP A1 protein. 3. Using PAR-CLIP with anti-hnRNP A1 antibody, hnRNP A1-bound RNA were subjected to miRNA, lncRNA, and circRNA-specific microarray. 17 miRNA, 8 lncRNA, and 18 circRNA were identified as candidates of hnRNP A1-binding ncRNA.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の進展によりhnRNP A1を介した固形がん悪性化機構の一端が明らかになり、更に飢餓状態下でhnRNP A1との結合が解離されるncRNAを同定する事につながる。このノンコーディングRNAの機能を検証する事で、新規機能性ncRNAの同定やこれらを標的にした新しいがん治療分子標的や診断・予後マーカー等を提示できる展望が開ける。この点は本邦の核酸医薬開発領域の更なる発展に貢献しうるものと考えられる。