Department of General Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
Department of Thyroid & Breast Surgery, The Affiliated Wuxi Hospital of Nanjing University of Traditional Chinese Medicine, Wuxi City Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, China.
Bioengineered. 2022 Mar;13(3):7771-7784. doi: 10.1080/21655979.2022.2047404.
Pancreatic cancer (PC) is a common type of malignancy originating from the epithelium of the pancreatic duct, with the most lethal feature and worst prognosis. LEM domain containing 1 (LEMD1) is overexpressed in multiple tumor tissues and plays a key role in cancer carcinogenesis and progression. However, little is known about the potential of LEMD1 in PC. In this study, we explored the clinical values, as well as the potential roles and mechanisms of LEMD1 in PC. We, for the first time, showed that LEMD1 was upregulated in PC and negatively correlated with the overall and disease-free survival of patients with PC. Of the function, LEMD1 knockdown inhibited cancer cell growth, migration and invasion, while LEMD1 overexpression promoted tumor aggressiveness. The tumor-promoting influences of LEMD1 in PC were also proved by in vivo assays. Mechanistically, GSEA identified that LEMD1 promoted PC aggressiveness, as well as affecting cell cycle dysregulation and apoptosis resistance, by p53 suppression and the activation of the mTORC1 signal pathway. In short, LEMD1 could serve as a valuable prognostic candidate and a potential therapeutic target of PC.: ATCC: American Type Culture Collection; CCK-8: Cell counting kit 8; CDK: Cyclin-dependent kinases; CTA: Cancer-testis antigen; DMEM: Dulbecco's Modified Eagle's Medium; ECL: enhanced chemiluminescence; FBS: Fetal bovine serum; GEO: Gene Expression Omnibus; LEMD1: LEM domain containing 1; mTOR: mammalian target of rapamycin; NC: Negative control; PC: Pancreatic cancer; PVDF: Polyvinylidene difluoride membranes; qRT-PCR: Quantitative real-time polymerase chain reaction; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; SD: Standard deviation; SKP2: S-Phase kinase-associated protein 2; TAA: Tumor-associated antigen; TBST: Tris-buffered Saline Tween-20; TCGA: The Cancer Genome Atlas.
胰腺导管上皮来源的恶性肿瘤常见，致死率最高，预后最差。富含亮氨酸重复序列和膜结构域蛋白 1（LEMD1）在多种肿瘤组织中高表达，在肿瘤发生和发展中起关键作用。然而，LEMD1 在胰腺导管腺癌（PC）中的潜在作用知之甚少。本研究首次探讨了 LEMD1 在 PC 中的临床价值及其潜在作用和机制。我们发现，LEMD1 在 PC 中上调，并与 PC 患者的总生存和无病生存呈负相关。功能上，敲低 LEMD1 抑制癌细胞生长、迁移和侵袭，而过表达 LEMD1 则促进肿瘤侵袭性。体内实验也证实了 LEMD1 在 PC 中的促瘤作用。机制上，GSEA 分析表明，LEMD1 通过抑制 p53 及激活 mTORC1 信号通路促进 PC 细胞的侵袭，影响细胞周期失调和抗凋亡。总之，LEMD1 可作为 PC 有价值的预后候选标志物和潜在治疗靶点。
