BBA advances
The long non-coding RNA LINC01089 facilitates prostate cancer progression
By Neira SV and Tang D.
Abstract
Background
Evidence suggests LINC01809 being involved in prostate cancer (PC). We studied LINC01089 functionality, the underlying mechanisms, and translational potential in PC.
Methods
Multiple PC cohorts (local, TCGA, and others) were utilized. Human (DU145 and LNCaP) and murine (TRAMP-C2) PC cells were used to investigate LINC01089-derived oncogenic potential in vitro and in vivo.
Results
LINC01089 upregulation occurred in PC, Gleason score 9-10 tumors and metastasis. LINC01089 stratified PC recurrence. Plasma collected from patients (n = 235) prior to treatment contained elevated LINC01089, which was further increased in higher Gleason PCs and modestly correlated with PSA score. LINC01089-positively correlated genes contained a 15-gene panel (Sig15) and were dominantly enriched in RNA splicing in multiple PC datasets, with three genes (DDX17, LUC7L3, and HNRNPH1/Overlap3) conserved. Overlap3 and Sig15 effectively stratified the recurrence risk of PC and poor prognosis across 9 other cancer types, and captured the tumors' RNA splicing property, a major mechanism contributing to androgen receptor (AR) variants. Ectopic LINC01089 enhanced DU145, LNCaP, and TRAMP-C2 PC cell proliferation, colony formation, and migration, and conferred LNCaP and TRAMP-C2 cell proliferation under androgen deprivation, along with AR upregulation in the nucleus. In C57BL/6 mice, TRAMP-C2 LINC01089 allografts grew faster and expressed increased nuclear AR, Ki67, and AKT activation. TRAMP-C2 LINC01089 allografts expressed higher levels of Overlap3 and some Sig15 genes.