Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and serious congenital disorder with poor outcomes, where a heterozygous missense mutation is present in the ACTG2 gene. Here, we aimed to investigate the pathogenesis of ACTG2 in MMIHS.
A cohort with 20 patients with MMIHS was screened. Actg2R257C heterozygous mutant mice were generated using the CRISPR/Cas9 system. Gastrointestinal (GI) motility, voluntary urination, collagen gel contraction, and G-actin/F-actin analysis were performed.
The R257C variant of ACTG2 most frequently occurred in patients with MMIHS and demonstrated the typical symptoms of MMIHS. Actg2R257C heterozygous mutant mice had dilated intestines and bladders. The functional assay showed a prolonged total time of GI transit and decreased urine spot area. Collagen gel contraction assay and G-actin/F-actin analysis indicated that mutant mice showed reduced area of contraction of smooth muscle cells (SMCs) and impaired actin polymerization.
A mouse model demonstrating MMIHS-like symptoms was generated. The Actg2R257C heterozygous variant impairs SMCs contraction by interfering with actin polymerization, leading to GI motility disorders.

Background Phenotypic switching in vascular smooth muscle cells (VSMCs) is involved in the pathogenesis of aortic dissection (AD). This study aims to explore the potential mechanisms of linc01278 during VSMC phenotypic switching. Methods and Results Twelve samples (6 AD and 6 control) were used for lncRNA, microRNA, and mRNA microarray analysis. We integrated the mRNA microarray data set with GSE52093 to determine the differentially expressed genes. Bioinformatic analysis, including Gene Expression Omnibus 2R, Venn diagram analysis, gene ontology, pathway enrichment, and protein-protein interaction networks were used to identify the target lncRNA, microRNA, and mRNA involved in AD. Subsequently, we validated the bioinformatics data using techniques in molecular biology in human tissues and VSMCs. Linc01278, microRNA-500b-5p, and ACTG2 played an important role in the vascular smooth muscle contraction pathway. Linc01278 and ACTG2 were downregulated and miR-500b-5p was upregulated in AD tissues. Molecular markers of VSMC phenotypic switching, including SM22α, SMA, calponin, and MYH11, were downregulated in AD tissues. Plasmid-based overexpression and RNA interference-mediated downregulation of linc01278 weakened and enhanced VSMC proliferation and phenotypic switching, respectively. Dual-luciferase reporter assays confirmed that linc01278 regulated miR-500b-5p that directly targeted ACTG2 in HEK293T cells. Conclusions These data demonstrate that linc01278 regulates ACTG2 to control the phenotypic switch in VSMCs by sponging miR-500b-5p. This linc01278-miR-500b-5p-ACTG2 axis has a potential role in developing diagnostic markers and therapeutic targets for AD.

Visceral myopathy is a rare genetic disorder that commonly affects the digestive and renal systems. Manifestations include a clinical spectrum covering chronic intestinal pseudo-obstruction (CIPO) and megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). The smooth muscle actin γ-2 gene (ACTG2) is one of the most common disease-causing genes. Here, we present a case of pediatric intestinal pseudo-obstruction associated with a novel missense ACTG2 mutation, c.588G>C/p.E196D. His parents had no this mutation, which suggested the possibility of spontaneous mutation. Amino acid conservation analysis of γ-2 actin showed replacement of glutamate at position 196 by aspartate. The patient suffered from recurrent episodes of abdominal bloating, undergone repeated gastrointestinal surgery, had feeding difficulties, and required long-term parenteral nutrition support. The patient had no other specific symptoms or underlying diseases. X-ray of the abdomen showed dilation of the intestine as well as an air-fluid pattern. The manifestations of biopsy were various. All biochemical tests were normal, and the possibility of secondary intestinal pseudo-obstruction was excluded. The mutation site of ACTG2 in the present study has not been previously described in patients with visceral myopathy, and thus, our study reveals a novel mutation of ACTG2-associated visceral myopathy in a patient with CIPO. This report can serve as a reference for future research and further expands the map of genetic variation for visceral myopathy.

Metastatic hepatocellular carcinoma (HCC) remains a mostly incurable disease. The fact that the identity of the mechanisms that regulate metastasis in HCC is known hampers the development of anti-metastatic therapies. Currently, there is no effective treatment for HCC once it is progressed to metastatic stage. Therefore, further study to elucidate the molecular mechanism underlying the metastasis of HCC is urgently required for the improvement of HCC treatment. Here, we describes actin gamma smooth muscle 2 (ACTG2) over-express in HCC and demonstrates high-expression of ACTG2 as a promising therapeutic target in HCC metastasis. The use of shRNA to knock-down ACTG2 impaired cells migration and invasion in vitro. Moreover, silencing of ACTG2 causes almost complete inhibition of metastasis in vivo. In contrast, overexpression ACTG2 significantly enforces HCC cells migration and metastasis. Finally, ACTG2 boosts the metastatic potential of HCC cells in a Notch homolog 1 (Notch1) dependent manner. Collectively, our study reveals a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC.