Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China.
Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China.
Acta Histochem. 2022 Apr;124(3):151874. doi: 10.1016/j.acthis.2022.151874. Epub 2022 Mar 15.
Clear cell renal carcinoma (ccRCC) is one of the most common malignant tumors worldwide. DNA damage-regulated autophagy modulator1 (DRAM1) plays an important roles in apoptosis and tumor progression. However, the role of DRAM1 in ccRCC is still unknown. In our study, we aimed to investigate the effect of DRAM1 in the progression of ccRCC.
The expression and prognostic information of DRAM1 in ccRCC were obtained by immunohistochemistry staining and bioinformatics database. Cell proliferation, migration, invasion were detected by CCK-8 assay, wound-healing and transwell assays, and the cell apoptosis was examined by tunel assay and flow cytometry analysis. Western blot was used to detect the expression of DRAM1, Bax, Bcl2, Akt, p53,E-cadherin, N-cadherin of ccRCC cells.
Decreased expression of DRAM1 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patient. We confirmed that DRAM1 inhibited the proliferation, migration, invasion and epithelial mesenchymal transformation (EMT), while enhanced the apoptosis of ccRCC cells. In addition, the results of inhibition of Akt signaling were consistent with the above. We further proved that DRAM1 over-expression decreased the phosphorylation of Akt signaling, and overexpression of DRAM1 could reverse oncogenic function induced by the over-activating of Akt in ccRCC cells.
overexpression of DRAM1 plays a tumor suppressive role in ccRCC through inactivation of Akt and highlights the potential role of DRAM1 as a prognostic biomarker in ccRCC.
透明细胞肾细胞癌（ccRCC）是全球最常见的恶性肿瘤之一。DNA 损伤调控自噬调节剂 1（DRAM1）在细胞凋亡和肿瘤进展中发挥重要作用。然而，DRAM1 在 ccRCC 中的作用尚不清楚。在本研究中，我们旨在研究 DRAM1 在 ccRCC 进展中的作用。
通过免疫组织化学染色和生物信息学数据库获得 DRAM1 在 ccRCC 中的表达和预后信息。通过 CCK-8 测定、划痕愈合和 Transwell 测定检测细胞增殖、迁移和侵袭，通过 tunel 测定和流式细胞术分析检测细胞凋亡。Western blot 用于检测 ccRCC 细胞中 DRAM1、Bax、Bcl2、Akt、p53、E-cadherin、N-cadherin 的表达。
发现 DRAM1 在 ccRCC 组织中表达下调，这预示着 ccRCC 患者的生存率较低。我们证实 DRAM1 抑制 ccRCC 细胞的增殖、迁移、侵袭和上皮间质转化（EMT），同时增强细胞凋亡。此外，抑制 Akt 信号的结果与上述结果一致。我们进一步证明，DRAM1 过表达降低了 Akt 信号的磷酸化，并且过表达 DRAM1 可以逆转 Akt 过度激活在 ccRCC 细胞中诱导的致癌功能。
DRAM1 的过表达通过失活 Akt 在 ccRCC 中发挥肿瘤抑制作用，并强调了 DRAM1 作为 ccRCC 预后生物标志物的潜在作用。
