Microeukaryotes play key roles in the structure and functioning of marine ecosystems. Little is known about the relative importance of the processes that drive planktonic and benthic microeukaryotic biogeography in subtropical offshore areas. This study compares the microeukaryotic community compositions (MCCs) from offshore waters (n = 12) and intertidal sediments (n = 12) around Xiamen Island, southern China, using high-throughput sequencing of 18S rDNA. This work further quantifies the relative contributions of spatial and environmental variables on the distribution of marine MCCs (including total, dominant, rare and conditionally rare taxa). Our results showed that planktonic and benthic MCCs were significantly different, and the benthic richness (6627 OTUs) was much higher than that for plankton (4044 OTUs) with the same sequencing effort. Further, we found that benthic MCCs exhibited a significant distance-decay relationship, whereas the planktonic communities did not. After removing two unique sites (N2 and N3), however, 72% variation in planktonic community was explained well by stochastic processes. More importantly, both the environmental and spatial factors played significant roles in influencing the biogeography of total and dominant planktonic and benthic microeukaryotic communities, although their relative effects on these community variations were different. However, a high proportion of unexplained variation in the rare taxa (78.1–97.4%) and conditionally rare taxa (49.0–81.0%) indicated that more complex mechanisms may influence the assembly of the rare subcommunity. These results demonstrate that patterns and processes in marine microeukaryotic community assembly differ among the different habitats (coastal water vs. intertidal sediment) and different communities (total, dominant, rare and conditionally rare microeukaryotes), and provide novel insight on the microeukaryotic biogeography and ecological mechanisms in coastal waters and intertidal sediments at local scale.

Aberrant N6-methyladenosine (m6A) modification has emerged as a driver of tumor initiation and progression, yet how long noncoding RNAs (lncRNA) are involved in the regulation of m6A remains unknown. Here we utilize data from 12 cancer types from The Cancer Genome Atlas to comprehensively map lncRNAs that are potentially deregulated by DNA methylation. A novel DNA methylation–deregulated and RNA m6A reader–cooperating lncRNA (DMDRMR) facilitated tumor growth and metastasis in clear cell renal cell carcinoma (ccRCC). Mechanistically, DMDRMR bound insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) to stabilize target genes, including the cell-cycle kinase CDK4 and three extracellular matrix components (COL6A1, LAMA5, and FN1), by specifically enhancing IGF2BP3 activity on them in an m6A-dependent manner. Consequently, DMDRMR and IGF2BP3 enhanced the G1–S transition, thus promoting cell proliferation in ccRCC. In patients with ccRCC, high coexpression of DMDRMR and IGF2BP3 was associated with poor outcomes. Our findings reveal that DMDRMR cooperates with IGF2BP3 to regulate target genes in an m6A-dependent manner and may represent a potential diagnostic, prognostic, and therapeutic target in ccRCC. Significance: This study demonstrates that the lncRNA DMDRMR acts as a cofactor for IGF2BP3 to stabilize target genes in an m6A-dependent manner, thus exerting essential oncogenic roles in ccRCC.

SummaryBenthic microeukaryotes are key ecosystem drivers in marine sandy beaches, an important and dynamic environment; however, little is known about their diversity and biogeography on a large spatial scale. Here, we investigated the community composition and geographical distributions of benthic microeukaryotes using high-throughput sequencing of the 18S rRNA gene and quantified the contributions of environmental factors and spatial separation on the distribution patterns of both rare and abundant taxa. We collected 36 intertidal samples at 12 sandy beaches from four regions that spanned distances from 0.001 to 12,000 km. We found 12,890 operational taxonomic units (OTUs; 97% sequence identity level) including members of all eukaryotic super-groups and several phyla of uncertain position. Arthropoda and Diatomeae dominated the sequence reads in abundance, but Ciliophora and Discoba were the most diverse groups across all samples. About onethird of the OTUs could not be definitively classified at a similarity level of 80%, supporting the view that a large number of rare and minute marine species may have escaped previous characterization. We found generally similar geographical patterns for abundant and rare microeukaryotic sub-communities, and both showed a significant distance-decay similarity trend. Variation partitioning showed that both rare and abundant sub-communities exhibited a slightly stronger response to environmental factors than spatial (distance) factors. However, the abundant subcommunity was strongly correlated with variations in spatial, environmental and sediment grain size factors (66% of variance explained), but the rare assemblage was not (16%). This suggests that different or more complex mechanisms generate and maintain diversity in the rare biosphere in this habitat.

Lysosome plays important roles in cellular homeostasis, and its dysregulation contributes to tumor growth and survival. However, the understanding of regulation and the underlying mechanism of lysosome in cancer survival is incomplete. Here, we reveal a role for a histone acetylation–regulated long noncoding RNA termed lysosome cell death regulator (LCDR) in lung cancer cell survival, in which its knockdown promotes apoptosis. Mechanistically, LCDR binds to heterogenous nuclear ribonucleoprotein K (hnRNP K) to regulate the stability of the lysosomal-associated protein transmembrane 5 (LAPTM5) transcript that maintains the integrity of the lysosomal membrane. Knockdown of LCDR, hnRNP K, or LAPTM5 promotes lysosomal membrane permeabilization and lysosomal cell death, thus consequently resulting in apoptosis. LAPTM5 overexpression or cathepsin B inhibitor partially restores the effects of this axis on lysosomal cell death in vitro and in vivo. Similarly, targeting LCDR significantly decreased tumor growth of patient-derived xenografts of lung adenocarcinoma (LUAD) and had significant cell death using nanoparticles (NPs)-mediated systematic short interfering RNA delivery. Moreover, LCDR/hnRNP K/LAPTM5 are up-regulated in LUAD tissues, and coexpression of this axis shows the increased diagnostic value for LUAD. Collectively, we identified a long noncoding RNA that regulates lysosome function at the posttranscriptional level. These findings shed light on LCDR/hnRNP K/LAPTM5 as potential therapeutic targets, and targeting lysosome is a promising strategy in cancer treatment.

The relative importance of different ecological processes that shape community structure is a central but poorly understood topic in protist ecology. This study used an 18S rRNA gene sequencing approach to examine the relative contributions of environmental selective (environmental filtering) and neutral processes (dispersal and ecological drift) in the community assembly of three diverse protist groups (Bacillariophyta, Cercozoa, and Ciliophora) from intertidal sediment samples spanning a geographical distance up to 12,000 km. All three protist communities exhibited similar and distinct biogeographical patterns, and followed strong distance-decay relationships at continental scale (ca. 12,000 km), regional scale (ca. 1500 km), and local scale (ca. 50 km). Network analysis showed that temperature, salinity, nitrite and nitrate nitrogen, total nitrogen, and 0.1-0.25 mm grain size together associated with 60.8%, 55.5%, and 50.0% of the OTUs, which represented 68.1%, 58.5%, and 59.2% of sequence abundances for Bacillariophyta, Cercozoa, and Ciliophora co-occurrence networks, respectively, indicating that these environmental variables played the central roles in influencing community composition. On the other hand, a neutral community model explained 73.6%, 64.2%, and 70.2% of community variation for Bacillariophyta, Cercozoa, and Ciliophora, respectively. More importantly, variation partitioning and partial Mantel tests showed that environmental selection exhibited a slightly greater influence on Ciliophora compared to spatial factors, but both components were roughly equivalent in Bacillariophyta and Cercozoa communities. Taken together, these results demonstrate that both environmental selection and neutral processes play important roles in creating the biogeographical patterns of protist communities in intertidal sandy beach ecosystems.