Background: Oral cancer remains a significant global health concern due to its high incidence and mortality, as highlighted by GLOBOCAN 2022, and is characterized by poor survival rates despite available therapies. Therefore, there is an imperative need for developing novel therapeutic targets for this disease. Methods: This study investigates the oncogenic role of mortalin in oral cancer. We have used The Cancer Genome Atlas (TCGA) dataset, samples from North Eastern Region of India and tissue microarray to examine the expression of this gene/protein in patient samples. siRNA related knock down studies were carried out to determine the role of mortalin on oral cancer cell proliferation, survival, metastases, EMT, autophagy etc. Results: Analysis of TCGA dataset revealed increased mortalin expression in head and neck squamous cell carcinoma (HNSCC), which correlated with tumor grade and stage, and was associated with diminished overall survival. These findings were validated in oral cancer patient tissue samples obtained from the North East Region of India and oral cancer cell lines. Functional assays showed that mortalin knockdown via siRNA reduced cancer cell proliferation, migration, invasion, and angiogenesis while inducing apoptosis, disrupting mitochondrial membrane potential, and modulating autophagy. These effects were linked to altered expression of regulatory molecules, including p53, p21WAF1, cyclins, caspases, MMPs, Survivin, and components of the Akt/mTOR pathway, thereby alleviating key hallmarks of oral cancer. Conclusion: Collectively, these data support mortalin as a potential therapeutic target for oral cancer and warrant further studies for the development of mortalin-targeting drugs in both laboratory and clinical settings.
背景：根据GLOBOCAN 2022数据，口腔癌因其高发病率和高死亡率仍是全球重大健康问题，其特征是尽管有现有疗法但生存率仍然较低。因此，迫切需要为此疾病开发新的治疗靶点。方法：本研究探讨了mortalin在口腔癌中的致癌作用。我们利用癌症基因组图谱（TCGA）数据集、印度东北部地区患者样本及组织芯片技术，检测了该基因/蛋白在患者样本中的表达情况。通过siRNA敲低实验，研究mortalin对口腔癌细胞增殖、存活、转移、上皮间质转化及自噬等过程的影响。结果：TCGA数据分析显示，头颈部鳞状细胞癌（HNSCC）中mortalin表达升高，其表达水平与肿瘤分级和分期相关，且与患者总生存期缩短存在关联。这些发现在印度东北部地区口腔癌患者组织样本及口腔癌细胞系中得到验证。功能实验表明，通过siRNA敲低mortalin可抑制癌细胞增殖、迁移、侵袭和血管生成，同时诱导细胞凋亡、破坏线粒体膜电位并调节自噬过程。这些效应与p53、p21WAF1、细胞周期蛋白、半胱天冬酶、基质金属蛋白酶、生存素及Akt/mTOR通路组分等调控分子的表达改变相关，从而缓解口腔癌的关键恶性特征。结论：综合而言，这些数据支持mortalin作为口腔癌潜在治疗靶点，并有必要在实验室和临床环境中进一步开展靶向mortalin的药物研发。
肿瘤(癌症)患者之家