Aging-US: HMGA1 promotes gastric cancer growth and metastasis07-25-2021
Aging-US published "HMGA1 promotes gastric cancer growth and metastasis by transactivating SUZ12 and CCDC43 expression" which reported that HMGA1 is overexpressed in GC cells and the high expression of HMGA1 was correlated with worse survival in GC patients using a bioinformatics assay.
Functionally, HMGA1 affected the EdU incorporation, colony formation, migration and invasion of GC cells by exogenously increasing or decreasing the expression of HMGA1.
Mechanistically, HMGA1 directly bound to the SUZ12 and CCDC43 promoter and transactivated its expression in GC cells.
Moreover, both HMGA1 and SUZ12/CCDC43 were highly expressed in cancer cells but not in normal gastric tissues, and their expressions were positively correlated.
Finally, a tail vein metastatic assay showed that HMGA1 promoted SUZ12/CCDC43-mediated GC cell metastasis in vivo.
These Aging-US findings suggest that HMGA1 promotes GC growth and metastasis by transactivating SUZ12 and CCDC43 expression, highlighting HMGA1 as a potential prognostic biomarker in the treatment of GC.
Dr. Li Xiang, Dr. Jide Wang, Dr. Side Liu and Dr. Weimei Tang said, "Gastric cancer (GC) is currently the fourth most common type of cancer worldwide and is the second cause of cancer-related deaths, with 738,000 deaths occurring every year across the globe."
HMGA1 is strongly expressed during embryogenesis and in virtually all aggressive human cancers but is silenced in adult, differentiated tissues.
Recent studies have shown that HMGA1 contributes to tumorigenesis in GC cancers.
SUZ12 is difficult to detect in normal tissues but is amplified and overexpressed in several solid cancers, such as breast, GC and head and neck squamous cell cancer.
Figure 6. SUZ12/CCDC43 is necessary for HMGA1-induced GC metastasis in vivo. (A) Whole-body fluorescence imaging of GC progression in mice (n = 3). Images of metastatic loci in the lungs by arrows. (B) Number of metastatic loci in lung was counted. ***, P < 0.01. (C) H&E staining of lungs was performed in samples from mice. (D) MMP7 expression in the lung metastasis of GC was detected by IHC. (E) Expression of MMP7 in lung tumours derived from AGS cells was determined by qRT-PCR. **, P < 0.05; ***, P < 0.01. Scale bars, 50 μm in (C, D).
Ectopic expression of the proteins in papillary thyroid carcinoma, lung cancer, cervical cancer, esophageal squamous cell carcinoma, pancreatic cancer and ovarian cancer has been shown to be related with the malignant behavior of human cancers.
Furthermore, HMGA1 promotes GC growth and metastasis by transactivating SUZ12 and CCDC43 expression.
The Xiang/Wang/Liu/Tang Research Team concluded in their Aging-US Research Output, "Taken together, this study provides convincing evidence that HMGA1 has an basic role in GC cell proliferation and metastasis by regulating the proto-oncogene SUZ12 or CCDC43. Thus, HMGA1 might become a potential favorable target for prevention of GC cell proliferation and metastasis.\”
Full Text - https://www.aging-us.com/article/203130/text
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.