Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
Institute of Oral Precancerous Lesions, Central South University, Changsha, China.
Cell Cycle. 2022 Mar;21(5):477-488. doi: 10.1080/15384101.2021.2021722. Epub 2022 Jan 4.
Proteasome 26S subunit, ATPase 2 (PSMC2) is a recently identified gene which is potentially associated with human carcinogenesis. However, the effects of PSMC2 on oral squamous cell carcinoma (OSCC) is still unclear. Here, we investigated PSMC2 expression in OSCC tissues and explored its effects on the biological behaviors of OSCC cells. PSMC2 expression was evaluated by immunohistochemistry in a tissue microarray containing 60 OSCC tissues and 9 normal tissues. PSMC2 was knocked down through lentivirus infection in OSCC cell lines. MTT, colony formation, flow cytometry, transwell, and scratch assays were performed to detect effects of PSMC2 knockdown on phenotypes of OSCC cells. Human apoptosis antibody array was used to screen potential downstream of PSMC2 in OSCC. Finally, the effects of PSMC2 knockdown on tumor growth were assessed in a tumor xenograft model using BALB/c nude mice. PSMC2 expression was significantly upregulated in OSCC tissues compared with normal tissues and correlated with poor prognosis. PSMC2 knockdown significantly suppressed cell proliferation, migration, but promoted apoptosis of OSCC cells. Additionally, we confirmed that PSMC2 knockdown can increase the expression of pro-apoptotic proteins. Furthermore, we found that PSMC2 knockdown downregulated expression of p100, p-Akt, CDK6, and upregulated of MAPK9. Xenograft experiments revealed that PSMC2 knockdown can suppress OSCC tumor growth and promote apoptosis. This study demonstrated that PSMC2 plays a critical role in OSCC progression through affecting pro-apoptotic protein expression and apoptosis pathways. It indicated that targeting PSMC2 might be a promising strategy for OSCC treatment.
蛋白酶体 26S 亚基，ATP 酶 2（PSMC2）是最近发现的一个基因，可能与人类癌变有关。然而，PSMC2 对口腔鳞状细胞癌（OSCC）的影响尚不清楚。在这里，我们研究了 PSMC2 在 OSCC 组织中的表达，并探讨了其对 OSCC 细胞生物学行为的影响。通过免疫组织化学方法在包含 60 例 OSCC 组织和 9 例正常组织的组织微阵列中评估 PSMC2 的表达。通过慢病毒感染在 OSCC 细胞系中敲低 PSMC2。通过 MTT、集落形成、流式细胞术、Transwell 和划痕实验检测 PSMC2 敲低对 OSCC 细胞表型的影响。使用人类凋亡抗体阵列筛选 PSMC2 在 OSCC 中的潜在下游靶点。最后，通过 BALB/c 裸鼠肿瘤异种移植模型评估 PSMC2 敲低对肿瘤生长的影响。与正常组织相比，PSMC2 在 OSCC 组织中表达显著上调，与不良预后相关。PSMC2 敲低显著抑制 OSCC 细胞的增殖、迁移，但促进凋亡。此外，我们证实 PSMC2 敲低可以增加促凋亡蛋白的表达。此外，我们发现 PSMC2 敲低可以下调 p100、p-Akt、CDK6 的表达，上调 MAPK9 的表达。异种移植实验表明，PSMC2 敲低可抑制 OSCC 肿瘤生长并促进凋亡。这项研究表明，PSMC2 通过影响促凋亡蛋白表达和凋亡途径在 OSCC 进展中发挥关键作用。这表明靶向 PSMC2 可能是治疗 OSCC 的一种有前途的策略。
