The transcription elongation factor TCEA3 induces apoptosis in rhabdomyosarcoma

Abstract

TCEA3 is one of three genes representing the transcription elongation factor TFIIS family in vertebrates. TCEA3 is upregulated during skeletal muscle differentiation and acts to promote muscle specific gene expression during myogenesis. Rhabdomyosarcoma (RMS) is a pediatric cancer derived from the muscle lineage, but the expression or function of TCEA3 in RMS was uncharacterized. We found that TCEA3 expression was strongly inhibited in RMS cell lines representing both ERMS and ARMS subtypes of RMS. TCEA3 expression correlates with DNA methylation and we show that TBX2 is also involved in the repression of TCEA3 in RMS cell lines. Ectopic expression of TCEA3 inhibited proliferation of RMS cell lines and initiated apoptosis through both the intrinsic and extrinsic pathways. We found that only pan-caspase inhibitors could block apoptosis in the presence of TCEA3. While expression of TCEA3 is highest in skeletal muscle, expression has been detected in other tissues as well, including breast, ovarian and prostate. We found that ectopic expression of TCEA3 also promotes apoptosis in HeLa, MCF7, MDA-231, and PC3 cell lines, representing cervical, breast, and prostate cancer, respectively. Restoration of TCEA3 expression in RMS cell lines enhanced sensitivity to chemotherapeutic drugs, including TRAIL. Thus, TCEA3 presents a novel target for therapeutic strategies to promote apoptosis and enhance sensitivity to current chemotherapeutic drugs.

USP47-Mediated Deubiquitination and Stabilization of TCEA3 Attenuates Pyroptosis and Apoptosis of Colorectal Cancer Cells Induced by Chemotherapeutic Doxorubicin

“…More recent studies showed that it is also expressed in many tissues, including muscle, adrenal prostrate, ovary, colon, and liver. It has been also found that TCEA3 was downregulated in a variety of cancers types, and the lower TCEA3 expression is associated shorter overall survival of cancer patients (Kazim et al, 2020).…”

“…More recent studies showed that it is also expressed in many tissues, including muscle, adrenal prostrate, ovary, colon, and liver. It has been also found that TCEA3 was downregulated in a variety of cancers types, and the lower TCEA3 expression is associated shorter overall survival of cancer patients ( Kazim et al, 2020 ). Our finding in this study that USP47 is able to deubiquitinate and stabilize TCEA3 indicates that the reduced expression of USP47 may play a significant role in the reduction of TCEA3 in cancers, and it is of great interesting to further identify the E2 and E3 that ubiquitinate TCEA3 in the future.…”

“…It has also been shown that knockdown of TCEA3 inhibited the proliferation of breast cancer cells and induces apoptosis ( Hubbard et al, 2008 ), indicating that the protein is required for the survival of cells. However, it has also been found that enforced expression of TCEA3 inhibited proliferation and induced apoptosis in a number lines of cancer cells, including RMS, HeLa, PC3, MCF7, and MDA-321 ( Kazim et al, 2020 ). In these cells, TCEA3 activated both intrinsic and extrinsic pathways of apoptosis.…”

Integrative Analysis of Multi-Omics Identified the Prognostic Biomarkers in Acute Myelogenous Leukemia

“…In an experiment on breast cancer cells, some scholars have found that inhibition of DNA methylation can accelerate the spread and metastasis of breast cancer cells ( 12 ). Some scholars have also found that the changes of DNA methylation and transcriptome are related to the sensitivity of chemotherapeutic drugs ( 13 , 14 ). Furthermore, scholars have found that cisplatin resistance is related to the hypermethylation deletion of several CpG sites mainly located in the intergenomic region, which directly affects the efficacy of treatment, thus affecting the survival time of patients ( 15 ).…”

Aberrant methylation of GADD45A is associated with decreased radiosensitivity in cervical cancer through the PI3K/AKT signaling pathway

“…Previous studies have reported that hypermethylation of DNA is observed in CC (22)(23)(24)(25). Currently, few reports have investigated the association between DNA methylation and radioresistance of CC (26,27).…”