Tex10 interacts with STAT3 to regulate hepatocellular carcinoma growth and metastasis

Abstract

Testis expression 10 (Tex10) is reported to be associated with tumorigenesis in several types of cancer types, but its role in hepatocellular carcinoma (HCC) metastasis has not been investigated. In this study, the expression of Tex10 in the HCC cell line and tissue microarray was determined by Western blot and immunohistochemistry (IHC), respectively. RNA sequencing‐based transcriptome analysis was performed to identify the Tex10‐mediated biological process. Cell Counting Kit‐8, colony formation, transwell assays, xenograft tumor growth, and lung metastasis experiments in nude mice were applied to assess the effects of Tex10 on cell proliferation, migration, invasion, and metastasis. The underlying mechanisms were further investigated using dual‐luciferase reporter, co‐immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. We found that Tex10 was upregulated in HCC tumor tissues compared to adjacent normal tissues, with its expression correlated with a poor prognosis. Gene ontology function enrichment analysis revealed alterations in several biological processes in response to Tex10 knockdown, especially cell motility and cell migration. Functional studies demonstrated that Tex10 promotes HCC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Moreover, Tex10 was shown to regulate invasion and epithelial–mesenchymal transition via signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, Tex10 was found to interact with STAT3 and promote its transcriptional activity. In addition, we found that Tex10 promotes p300‐mediated STAT3 acetylation, while p300 silencing abolishes Tex10‐enhanced STAT3 transcriptional activity. Together, these findings indicate that Tex10 functions as an oncogene by upregulating STAT3 activity, thus suggesting that Tex10 may serve as a prognostic biomarker and/or therapeutic target for HCC patients.

The impact of ribosome biogenesis in cancer: from proliferation to metastasis

“…Furthermore, in addition to its involvement in rRNA processing, PELP1 is recruited to rDNA promoters to facilitate rRNA transcription, suggesting its dual roles in promoting ribosome biogenesis ( 154 ). Interestingly, other components of the Rix1 complex (WDR18 and TEX10) are also found overexpressed in cancer, indicating that the function of this complex is required to support high rates of ribosome biogenesis in cancer ( 140 , 155 , 156 ). While there are clear indications of PELP1's involvement in cancer proliferation and progression, its precise impact on cancer development via ribosome biogenesis, rather than hormone receptor activity regulation, remains largely unexplored.…”