Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam.
BMC Cancer. 2021 Jun 26;21(1):737. doi: 10.1186/s12885-021-08477-1.
Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC).
To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2.
RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells.
Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words).
色氨酸 2,3-双加氧酶(TDO2)是分解色氨酸的主要酶。有几条证据表明,TDO2 的过表达与抗失巢凋亡、球体形成、增殖、侵袭有关,并与某些癌症的预后不良相关。本研究旨在揭示 TDO2 在肾细胞癌(RCC)中的表达和生物功能。
为了展示 TDO2 在 RCC 中的表达,我们进行了 qRT-PCR 并结合 TCGA 数据分析进行了免疫组织化学分析。评估了 TDO2 与 PD-L1、CD44、PTEN 的相互作用以及 TDO2 的表达。我们探讨了敲低 TDO2 对 RCC 细胞系增殖、集落形成和侵袭的影响。
RNA-Seq 和免疫组织化学分析表明,TDO2 在 RCC 组织中表达上调,与疾病进展和 RCC 患者的不良生存相关。此外,TDO2 与 PD-L1 和 CD44 共表达。在 RCC 细胞系中进行的计算机分析和 PTEN 的体外敲除揭示了 PTEN 调节 TDO2 表达的能力。敲低 TDO2 抑制了 RCC 细胞的增殖和侵袭。
我们的结果表明,TDO2 可能在疾病进展中发挥重要作用,并且可能是 RCC 靶向治疗的有前途的标志物。(199 个单词)