ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most fatal malignant tumors worldwide. Circular RNAs (circRNAs) are a special type of RNA that lacks the 5' and 3' ends. The functional roles of circRNAs in HCC remain largely unknown. Using high-throughput sequencing, we found several differentially expressed circRNAs in HCC tissues compared with nearby normal tissues. Among them, circRNA derived from the LIFR gene, named circLIFR, was significantly downregulated in HCC. Intriguingly, circLIFR overexpression in SK-Hep-1 cells promoted cell growth and invasion. RNA pull-down and mass spectrometry detection revealed circLIFR interacting with TANK binding kinase 1 (TBK1). Anti-TBK1 RIP confirmed the interaction between circLIFR and TBK1. TBK1 is a serine/threonine kinase that regulates several signaling pathways, including the NF-κB pathway. TBK1 inhibitors inhibit NF-κB activation. Overexpression of circLIFR overcame the in-hibitory function of TBK1, resulting in the upregulation of several genes, including MMP13, MMP3, VEGF, and MAPK. This study shows that the downregulation of circLIFR in HCC has a can-cer-promoting effect by interacting with TBK1 to promote the activation of downstream NF-κB pathway genes related to cell proliferation, migration, and invasion. This novel finding reveals the diversity of circRNA functions in HCC and provides novel insights into the role of circRNAs.
ABSTRACT
Early ripening in grape (Vitis vinifera L.) is a crucial agronomic trait. The fruits of the grape line 'Summer Black' (SBBM), which contains a bud mutation, can be harvested approximately one week earlier than the 'Summer Black' (SBC)control. To investigate the molecular mechanism of the bud mutation related to early ripening, we detected genome-wide genetic variations based on re-sequencing. In total, 3,692,777 single nucleotide polymorphisms (SNPs) and 81,223 structure variations (SVs) in the SBC genome and 3,823,464 SNPs and 85,801 SVs in the SBBM genome were detected compared with the reference grape sequence. Of these, 635 SBC-specific genes and 665 SBBM-specific genes were screened. Ripening and colour-associated unigenes with non-synonymous mutations (NS), SVs or frame-shift mutations (F) were analysed. The results showed that 90 unigenes in SBC, 76 unigenes in SBBM and 13 genes that mapped to large fragment indels were filtered. The expression patterns of eight genes were confirmed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).The re-sequencing data showed that 635 SBC-specific genes and 665 SBBM-specific genes associated with early ripening were screened. Among these, NCED6 expression appears to be related to NCED1 and is involved in ABA biosynthesis in grape, which might play a role in the onset of anthocyanin accumulation. The SEP and ERF genes probably play roles in ethylene response.
