Circular RNA (CircRNA) is a newly identified special class of non-coding RNA (ncRNA) that plays an important regulatory role in the progression of certain diseases. Herein, our results indicate that CircMEG3 is downregulated expression and negatively correlated with the expression of telomerase-related gene Cbf5 in human liver cancer. Moreover, CircMEG3 inhibits the growth of human liver cancer stem cells in vivo and in vitro. CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of Cbf5, a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. Thereby, CircMEG3 inhibits telomerase activity and shortens telomere lifespan dependent on HULC and Cbf5 in human liver cancer stem cell. Strikingly, increased Cbf5 abrogates the ability of CircMEG3 to inhibit malignant differentiation of human liver cancer stem cells. In summary, these observations provide important basic information for finding effective liver cancer therapeutic targets.

Summary miR-1307 is highly expressed in liver cancer and inhibits methyltransferase protein8. Thereby, miR-1307 inhibits the expression of KDM3A and KDM3B and increases the methylation modification of histone H3 lysine 9, which enhances the expression of endoplasmic-reticulum-related gene CALR. Of note, miR-1307 weakens the binding ability of OSTC to CDK2, CDK4, CyclinD1, and cyclinE and enhances the binding ability of CALR to CDK2, CDK4, CyclinD1, and cyclinE, decreasing of p21WAF1/CIP1, GADD45, pRB, and p18, and decreasing of ppRB. Furthermore, miR-1307 increases the activity of H-Ras, PKM2, and PLK1. Strikingly, miR-1307 reduces the binding ability of OSTC to ATG4 and enhances the binding ability of CALR to ATG4. Therefore, miR-1307 reduces the occurrence of autophagy based on ATG4-LC3-ATG3-ATG7-ATG5-ATG16L1-ATG12-ATG9- Beclin1. In particular, miR-1307 enhances the expression of PAK2, PLK1, PRKAR2A, MYBL1, and Trim44 and inhibits the expression of Sash1 and Smad5 via autophagy. Our observations suggest that miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway.

Recent metagenomics studies have identified a novel archaeal superphylum namely Asgard, which are characterized by enriched eukaryotic-specific proteins. In this study, we screened unclassified archaeal genomes in public databases and obtained a high-qualified metagenome-assembled genome that can be assigned as a novel family-level Asgard member namely Odinarchaeceae Tengchong. Metabolic analysis indicates an autotrophic lifestyle of this hot spring archaeon with a complete tetrahydromethanopterin Wood-Ljungdahl pathway for carbon dioxide reduction and an arsenic efflux detoxification. Examination of public databases found that thus far Odinarchaeceae Tengchong may be the only prokaryote that encodes a C-terminal domain of Vps28 in the endosomal sorting complex required for transport (ESCRT), a critical connector of multiple ESCRT components. Therefore, the identification of this archaeon provides valuable evidence of the archaeal origin of eukaryotic ESCRT. We posit that all the key components of the eukaryotic endosomal system might have evolved from a common ancestor of Asgard archaea and eukaryotes.

Background: Although miR-26a-1 was down-regulated expressin in several cancers, the role of miR-26a-1in malignancies has yet to be systematically elucidated. Methods: RT-PCR, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: miR-26a-1 inhibits the NAD(+)-dependent deacetylase Sirt1 expression by targeting the 3' non-coding region of Sirt1 which enhances the acetylation modification of H4 on the 16th lysine of histone and the expression of protein arginine methyltransferase PRMT6. Therefore, miR-26a-1 promotes arginine methylation modification of POLB (R137) and histone. On the other hand, miR-26a-1 inhibits the expression of KDM5A by targeting its 3' non-coding region, which enhances the methylation modification of histone H3 ysine 4. Moreover, miR-26a-1 enhances the expression of histone methyltransferase SETD2 dependent on H3K4me3 and further increases the trimethylation modification of the histone H3 lysine 36 . Significantly, miR-26a-1 promotes the formation of DNA damage repair complex (Rad51-PARP1-ATR-ATM-hMSH6-XRCC-POLB-SKP2) via H3K36me3. In particular, it was found that miR-26a-1 inhibited the function of long non-coding RNA HULC and promoted the formation of DNA damage repair complex. Furthermore, miR-26a-1 promotes the DNA damage repair ability by promoting the DNA damage repair complex to bind to the DNA damage site, thereby inhibiting the DNA damage of liver cancer stem cells. In particular, miR-26a-1 enhanced the binding of H3F3A to Skp2, CUL1, and F-box at the DNA damage site and enhanced the protein ubiquitination modification of H3F3A, which promoted Histone H3 replaces H3F3A by degrading H3F3A, realizing the renewal of histones after DNA damage repair. It was further found that miR-26a-1 inhibited the formation and instability of DNA microsatellites by promoting DNA damage repair, thereby affecting the expression of several cyclins and protein kinases in liver cancer stem cells, such as, inhibiting CDK2 and CyclinE , CDK4, CyclinD1, CDK6, CDK8, CyclinM2, CDK15, pRB, PCNA, MAP3K2, PGK1 and promoting RB, P18, P21/WAF1/Cip1, and thus inhibited the growth of liver cancer stem cells. Strikingly, the rescued-test further confirmed that excessive Sirt1 and KDM5A abrogated the oncogenic function of miR-26a-1. Conclusions: miR26a-1 may acts as the potential biomarker and therapeutic target for liver cancer.

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