An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression

Abstract Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958 individuals and identify rs73613962 (T > G) within the intronic region of PRMT7 at 16q22.1 as a susceptibility locus of HCC (OR = 1.41, P = 6.02 × 10⁻¹⁰). An enhancer dual-luciferase assay indicates that the rs73613962-harboring region has allele-specific enhancer activity. CRISPR-Cas9/dCas9 experiments further support the enhancer activity of this region to regulate PRMT7 expression. Mechanistically, transcription factor HNF4A binds to this enhancer region, with preference to the risk allele G, to promote PRMT7 expression. PRMT7 upregulation contributes to in vitro, in vivo, and clinical HCC-associated phenotypes, possibly by affecting the p53 signaling pathway. This concept of HCC pathogenesis may open a promising window for HCC prevention/treatment

Finite dispersal of a separative nepheloid plume by an internal hydraulic jump in a tropical mountainous river estuary

This paper investigates the dynamics of an internal hydraulic jump in a river plume and associated suspended sediment dispersal. Field investigations were undertaken into the river plume generated by the Herbert River, Australia, following a moderate flood event induced by Cyclone Fritz in 2004. The forced plume experiences an abrupt transition from supercritical to subcritical via an internal hydraulic jump, as defined by a mode-1 internal Froude number computed using the phase speeds from the Taylor-Goldstein equation. The hydraulic theory of a two-layer stratified flow was used to identify the plume shape and the mechanical energy loss within the jump. The hydraulic jump energy loss is primarily transferred to the buoyancy-driven potential energy, uplifting the river plume. Intense stratification decreases the bottom stress, damping the resuspension. Therefore, a separative nepheloid dispersal system occurs at the jump section. Both the upper and lower nepheloid flows are confined to the inner shelf, but have different dispersal behaviors and mechanisms. The upper nepheloid flow, which is primarily controlled by advection and settling, satisfies an exponential decay law of the total suspended sediment concentrations versus the offshore distance. The lower nepheloid flow dominated by deposition is detached seaward near the lift-off point of the river plume. A turbidity front associated with the jump may accumulate a large quantity of suspended sediments, enhancing sediment release from the river plume. These findings will promote in-depth understanding of both the cross-shelf sediment dispersal and muddy deposit on the shelf