Alternative Splicing of lncRNAs From SNHG Family Alters snoRNA Expression and Induces Chemoresistance in Hepatoblastoma

• DOI: 10.1016/j.jcmgh.2023.07.007
• Publication Date: 2023-07-19T07:02:59Z
• Authors: Ni Zhen; Jiabei Zhu; Siwei Mao; Qi Zhang; Song Gu; Ji Ma; Yue Zhang; Minzhi Yin; Haojie Li; Nan Huang; Han Wu; Fenyong Sun; Binwu Ying; Lin Zhou; Qiuhui Pan
• Keywords: Small nucleolar RNA; Hepatoblastoma; Splicing factor

Background & AimsHepatoblastoma (HB) is a common pediatric malignant liver tumor that characterized by low level of genetic mutations. Alternative splicing (AS) has been shown to be closely associated with cancer progression, especially in tumors mutational burden. However, the role AS HB remains unknown.MethodsTranscriptome sequencing was performed on 5 pairs tissues and matched non-tumor delineate landscape HB. events were validated 92 samples from 46 patients. RNA pull-down immunoprecipitation assays carried out identify factors regulate small nucleolar host genes (SNHG). Patient-derived organoids (PDOs) established investigate factor polyadenylate-binding nuclear protein 1 (PABPN1).ResultsThis study uncovered aberrant alternative HB, including lncRNAs SNHG family undergo intron retention Further investigations revealed PABPN1, significantly upregulated binding protein, interacts machinery inducing these RNAs downregulation intronic (snoRNAs). Functionally, PABPN1 acts as an oncofetal regulator promoting cell proliferation DNA damage repair via SNHG19. Knock-down increases cisplatin sensitivity PDOs.ConclusionsOur findings regulating snoRNA expression hepatoblastoma, explained detailed regulatory mechanism between RNAs, provided insight into development new treatment options. Hepatoblastoma unknown. Transcriptome (PABPN1). This PDOs. Our