Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer

Abstract

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the ACTG1 functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies.

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

“…However, FCRL4, usually expressed on the memory B cells under infection, it’s overexpression also could impede antigen-induced BCR signaling 43 . Besides, ACTG1 44 and FAM3C 45 46 , which were reported to promote tumor development, were also up-regulated in this cluster. For B-c3, it was defined as follicular B cells for the expression of IGHD and FCER2.…”

Immunological significance of alternative splicing prognostic signatures for bladder cancer

“…We established a BLCA prognostic signature based on 7 AS events, in which C19orf57|47943|ES, ACTG1|44120|RI, DYM|45472|ES and HPCAL1|52658|ES were protective AS events, and ANK3|11845|AP, GRIK2|77096|AT and PTGER3|3415|AT were dangerous AS events. ACTG1 is overexpressed in uterine cancer cells, and shows an inhibitory response to immunotherapy [52]. Aerobic glycolysis inhibits the proliferation of hepatocellular carcinoma (HCC) cells by downregulating ACTG1, and a high level of ACTG1 is significantly related to advanced hepatoma [53].…”

Actin gamma 1 is a critical regulator of pancreatic ductal adenocarcinoma

“…[ 9 26 ] Similarly, uterine cancers harbored 5%–20% of ACTG1 gene amplification or overexpression, whose higher expression was correlated with unfavorable prognosis. [ 27 ] Intriguingly, bioinformatic analyses revealed that high expression of ACTG1 may promote colon adenocarcinoma cell growth, but was relative to higher survival rate. [ 28 ] Therefore, detailed and specific roles of ACTG1 in distinct cancer types needs further investigation.…”