Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

Abstract

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear lamina, where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9.

Nuclear Lamins and Emerin Are Differentially Expressed in Osteosarcoma Cells and Scale with Tumor Aggressiveness

“…Starting from the observation that lamin A/C was strongly correlated to the aggressiveness of osteosarcoma cell lines, the expression of this nucleoskeleton protein in histological samples has provided a prognostic significance for lamin A/C expression, pointing out that the high lamin A/C staining can be considered as a "good prognosis" predictor in osteosarcoma patients. These data are in accordance with other works in the literature in which the reduction of lamin A/C expression is correlated to an increased aggressiveness of the tumor [55][56][57].…”

Expression and prognostic value of E2F3 transcription factor in non‑small cell lung cancer

“…Numerous advances have been made in the molecular diagnosis of lung cancer; however, the survival rate of patients with this malignant tumor remains low ( 20 ). Therefore, the identification of new biomarkers is important to improve the subclassification of NSCLC for the planning of appropriate treatment, and establishment of a prognostic evaluation system ( 21 ).…”

miR-9-5p Exerts a Dual Role in Cervical Cancer and Targets Transcription Factor TWIST1

“…TWIST1 mediates EMT by transcriptional suppression of epithelial protein CDH1 and transcriptional activation of mesenchymal marker CDH2 [44][45][46][47]. Interestingly, CDH1 has also been established as a direct target of miR-9-5p in a multitude of human cancers [12,16,[37][38][39][40][41]. In cervical cancer, downregulation of CDH1 has been observed [58][59][60].…”

“…Cancerous epithelial cells achieve anchorage independence by induction of epithelial-tomesenchymal transition (EMT), thereby overcoming detachment-induced cell death (anoikis) [36]. MiR-9-5p has previously been implicated in this process by targeting CDH1 [12,16,[37][38][39][40][41]. Interestingly, using TargetScan v7 [42] and RNA22 v2.0 [43] algorithms we identified transcription factor and EMT regulator TWIST1 as a novel potential miR-9-5p target.…”