Lamin B1 is a potential therapeutic target and prognostic biomarker for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy. Previous studies have found that lamin B1 (LMNB1) contributes to the development of human cancers. However, the biological functions and prognostic values of LMNB1 in HCC have not been adequately elucidated. In our present research, the expression pattern of LMNB1 was analyzed. The prognostic values of LMNB1 were evaluated by Kaplan–Meier survival analysis and Cox proportional hazards regression analysis. The effects of LMNB1 on HCC progression were assessed by Cell Counting Kit-8 (CCK-8), colony formation, wound healing, Transwell and in vivo xenograft assays. The mechanisms of LMNB1 in HCC progression were elucidated by gene set enrichment analysis (GSEA) and loss-of-function assays. Besides, a nomogram for predicting overall survival (OS) was constructed. The results demonstrated that LMNB1 was overexpressed in HCC and that increased LMNB1 expression predicted a dismal prognosis. Further experiments showed that LMNB1 facilitated cell proliferation and metastasis in HCC. Functional enrichment analysis revealed that LMNB1 modulated metastasis-associated biological functions such as focal adhesion, extracellular matrix, cell junctions and cell adhesion. Mechanistically, we revealed that LMNB1 promoted HCC progression by regulating the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Moreover, incorporating LMNB1, Ki67 and Barcelona Clinic Liver Cancer (BCLC) stage into a nomogram showed better predictive accuracy than the Tumor-Node-Metastasis (TNM) stage and BCLC stage. In conclusion, LMNB1 may serve as an effective therapeutic target as well as a reliable prognostic biomarker for HCC.

A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

“…LMNB1 is an oncogene in various cancers. In HCC, our previous study demonstrated that silencing of LMNB1 inhibited HCC proliferation and metastasis both in vitro and in vivo [39]. Another study reported that circulating LMNB1 is a diagnostic biomarker for early stage liver cancer [15].…”

CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR‐140‐5p/LMNB1 axis

“… 41 , 42 , 43 , 44 , 45 In addition, LMNB1 also plays an important role in tumor progression, and the biological function of LMNB1 is closely related to the abnormal proliferation and potential tumorigenicity of tumor cells. For example, LMNB1facilitates cell proliferation, EMT, and metastasis in hepatocellular carcinoma, 46 LMNB1 promotes lung adenocarcinoma cell proliferation through the AKT pathway. 47 Most importantly, LMNB1 is a potential therapeutic target for betulinic acid in PDAC, 48 but the molecular mechanism by which LMNB1 promotes PDAC progression is unclear.…”

Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment

“…Several studies provided evidence linking the dysregulated expression of these 10 classifier genes to adverse outcomes in HCC, including poor prognosis, increased proliferation, metastasis, and recurrence [43][44][45][46][47][48][49][50]. Notably, these genes showed significant expression differences between different subtypes and normal samples (Fig 5E and 5F), indicating their crucial…”