LncRNA-Encoded Micropeptide ACLY-BP Drives Lipid Deposition and Cell Proliferation in Clear Cell Renal Cell Carcinoma via Maintenance of ACLY Acetylation

Author:

Zhang Shenghua123ORCID,Zhang Zheng1ORCID,Liu Xiaolong4ORCID,Deng Yibin3ORCID,Zheng Jian5ORCID,Deng Jieqiong1ORCID,Wang Yirong1ORCID,Guo Binbin1ORCID,Li Fanrong1ORCID,Chen Xiaoyue1ORCID,Pan Yacheng1ORCID,Wang Jieyu1ORCID,Lu Jiachun6ORCID,Wu Siqi1ORCID,Guo Qiang2ORCID,Zhou Yifeng123ORCID

Affiliation:

1. 1Department of Genetics, Medical College of Soochow University, Suzhou, Jiangsu, China.

2. 2Institute of Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University (Suzhou Dushu Lake Hospital); Medical College of Soochow University, Suzhou, Jiangsu, China.

3. 3Clinic Medicine Research Center of Hepatobiliary Diseases, Centre for Medical Laboratory Science, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.

4. 4Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

5. 5State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

6. 6The Institute for Chemical Carcinogenesis, The First Affiliated Hospital, The School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong, China.

Abstract

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common subtype of lethal kidney cancer. Reprogramming of fatty acid and glucose metabolism resulting in the accumulation of lipids and glycogen in the cytoplasm is a hallmark of ccRCC. Here, we identified a micropeptide ACLY-BP encoded by the GATA3-suppressed LINC00887, which regulated lipid metabolism and promoted cell proliferation and tumor growth in ccRCC. Mechanistically, the ACLY-BP stabilizes the ATP citrate lyase (ACLY) by maintaining ACLY acetylation and preventing ACLY from ubiquitylation and degradation, thereby leading to lipid deposition in ccRCC and promoting cell proliferation. Our results may offer a new clue for the therapeutic approaches and the diagnostic assessment for ccRCC. Implications: This study identifies ACLY-BP encoded by LINC00887 as a lipid-related micropeptide that stabilizes ACLY to generate acetyl-CoA, driving lipid deposition and promoting cell proliferation in ccRCC.

Funder

National Science Fund for Distinguished Young Scholars

National Natural Science Foundation of China

Guangdong Province Introduction of Innovative R&D Team

Natural Science Foundation of Guangxi Province

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology,Molecular Biology

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