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Background: Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. Methods: The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6‐methyladenosine (m6A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me‐RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull‐down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6‐encoded protein was verified by mass spectrometry. Results: CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6‐144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6A‐dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6‐144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. Conclusion: Collectively, our study reveals that m6A‐modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6‐144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis, and novel treatment strategies are urgently needed. Mitochondria are key regulators of cellular homeostasis and potential targets for tumor therapy. Here, the role of mitochondrial translocator protein (TSPO) in the regulation of ferroptosis and antitumor immunity is investigated and the potential therapeutic implications for HCC are assessed. TSPO is highly expressed in HCC and associated with poor prognosis. Gain‐ and loss‐of‐function experiments present that TSPO promotes HCC cell growth, migration, and invasion in vitro and in vivo. In addition, TSPO inhibits ferroptosis in HCC cells via enhancing the Nrf2‐dependent antioxidant defense system. Mechanistically, TSPO directly interacts with P62 and interferes with autophagy, leading to the accumulation of P62. The P62 accumulation competes with KEAP1, preventing it from targeting Nrf2 for proteasomal degradation. Furthermore, TSPO promotes HCC immune escape by upregulating PD‐L1 expression through Nrf2‐mediated transcription. Notably, TSPO inhibitor PK11195 combines with anti‐PD‐1 antibody showing a synergistic anti‐tumor effect in a mouse model. Overall, the results demonstrated that mitochondrial TSPO promotes HCC progression by inhibiting ferroptosis and antitumor immunity. Targeting TSPO can be a promising new strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

The potential interactions between aeolian and fluvial systems are critical in understanding environmental change. Whether aeolian products originated from the river depends on the river characteristics and wind regimes. In southern Tibet, aeolian sand dunes are widespread along the Yarlung River, and thus provide an ideal example to explore the relationships between large fluvial systems and aeolian products. Although previous studies postulated that those aeolian products were originated from the Yarlung River, few empirical data actually exist to support this idea. We analysed the spatial pattern, sand transportation directions, and granulometric characteristics of the sand dunes to evaluate the potential influence of the Yarlung River on the aeolian processes. Comparison of the dune field distribution against channel width and longitudinal profile of the Yarlung River shows that sand dunes are clustered at the wide and flat segments of the river. Analyses of >4,600 sand dune orientations using Google Earth imagery show that the dunes located at the southern and northern sides of the Yarlung River demonstrate opposite sand transportation directions that generally point against the river. This suggests that the sand grains probably originated from the river. Grain size distributions from dune samples show unimodal or unimodal‐like patterns. This means that each sand dune field was dominantly fed by a simple transportation process rather than by compound processes from smaller‐level fluvial systems, which in turn implies that the Yarlung River was the most possible candidate for the provenance of these aeolian deposits. This study provides new constraints to demonstrate that the Yarlung River provides both accommodation space and sorted fluvial sand for the aeolian sand dunes along the river. [ABSTRACT FROM AUTHOR]

The development and transformation of barchan-parabolic dune can be led by vegetationestablishment, which may be induced by climate change (precipitation, temperature, andwind strength) and/or human intervention. The impact of wind strength change-inducedvegetation restoration on dunes morphology and theirs surface sedimentary features isneglected in the Maowusu Sandy Land. In this study, we combined datasets of NormalizedDifference Vegetation Index (NDVI) and climatic factors to analyze temporal changes invegetation growth and their response to changes in temperature, precipitation and windstrength in the northern margin of Maowusu Sandy Land from 1982 to 2015. Growing seasonNDVI is related to the significant decrease in drift potential (DP) during the entire studyperiod. Further temporal analyses indicate that the growing season NDVI trends are largelycontributed by wind strength and temperature changes during the earlier study period1982-2006. And then, the increasing NDVI is consistent with the slightly increasing trend ofprecipitation during the recent study period 2006-2015. Thus, the transformation ofthe transitional dune cannot be explained by the increasing trend of wind strengthchange-induced vegetation alone. During the recent period, once dunes are covered byvegetation, the change in wind strength cannot mobilize the stable dunes becausethe vegetation provides an effective buffer preventing sand erosion. To reveal theresponse of sedimentological reorganization during the dune transformation processes,grain-size characteristics along the longitudinal profile of three different types of duneswere examined. From barchan dune through transition dune to parabolic dune, withthe increase of the fine sands (125-250μm) proportions, the mean grain size MZgradually decreases; in addition, as the very fine sands (<125μm) class increases, thesorting σ1 of sand dunes gradually became worse. The decreasing wind strengthlead to partly transport of fine sands on the upper part of dune windward slope,resulting in the progress coarsening and the reduction of dune height at the crestarea. No distinct trend in sorting and mean grain size on the windward slope oftransition dune, indicating that sand in transport had little influence on the particle sizedistributions. Conversely, the progressive of sorting and coarsening of sands towards thecrest of parabolic dune, implying that vegetation limited the sands from upwind ofdune, changed the effective source of dune into the underlying source deposits orreworking pre-existing aeolian deposits and trapped the sands on the crest area. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC., Methods: The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N 6 -methyladenosine (m 6 A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me-RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull-down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6-encoded protein was verified by mass spectrometry., Results: CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6-144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m 6 A-dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6-144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself., Conclusion: Collectively, our study reveals that m 6 A-modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6-144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC., Significance: This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target., (©2021 American Association for Cancer Research.)