Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression

Zhang，Qiangnu1,2; Wei，Teng3; Yan，Lesen1; Zhu，Siqi1; Jin，Wen4; Bai，Yu1; Zeng，Yuandi1; Zhang，Xiao Fei5; Yin，Zexin1; Yang，Jilin1; Zhang，Wenjian1; Wu，Meilong1; Zhang，Yusen1; Liu，Liping1

2023-08-01

10.1158/0008-5472.CAN-23-0337

Cancer Research   Impact Factor & Quartile

0008-5472

1538-7445

Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619–22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619–22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N-methyladenosine (mA) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619–22aa reduced global mA levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC.

SCI

English

NI Journal Papers

First ; Corresponding

China Postdoctoral Science Foundation[2021M701426];National Natural Science Foundation of China[8140204];National Natural Science Foundation of China[82002956];

Oncology

Oncology

WOS:001045209900001

AMER ASSOC CANCER RESEARCH

CLINICAL MEDICINE

2-s2.0-85166393718

Scopus

1.Division of Hepatobiliary and Pancreas Surgery,Department of General Surgery,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
2.Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou,China
3.Cytotherapy Laboratory,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University,the First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
4.Department of Neurology,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University; the First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
5.Beijing Key Laboratory of Microstructure and Properties of Solids,Institute of Microstructure,Property of Advanced Materials,Faculty of Materials and Manufacturing,Beijing University of Technology,Beijing,China

Zhang，Qiangnu,Wei，Teng,Yan，Lesen,et al. Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression[J]. Cancer Research,2023,83(15):2496-2512.

Zhang，Qiangnu.,Wei，Teng.,Yan，Lesen.,Zhu，Siqi.,Jin，Wen.,...&Liu，Liping.(2023).Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression.Cancer Research,83(15),2496-2512.

Zhang，Qiangnu,et al."Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression".Cancer Research 83.15(2023):2496-2512.