Abstract
Prostate cancer (PCa) is the second leading cause of cancer death in men. Irradiation is one of the available options for treatment of PCa, however, approximately 10–45% of PCa are resistant to irradiation. We aimed to explore the role of long non-coding RNA highly upregulated in liver cancer (HULC) in the sensitivity of PCa cells to irradiation. Survival rate, cell apoptosis, cycle, expressions of related proteins, and caspase-3 activity were assessed to explore the effects of HULC on sensitivity of PCa cells to irradiation. Expression of HULC in DU-145, PC3, LNCaP, and RWPE-1 cells was determined and the influence of HULC on DU-145 cells was explored. Then, PC3 cells aberrantly expressing HULC were implanted into NOD-SCID mice for tumor xenograft study. Changes of autophagy after aberrant expression of HULC in vivo and in vitro were tested. Furthermore, the interacted protein of HULC and involved signaling pathway were investigated. In PC3 and LNCaP cells under irradiation, survival rate and cell cycle were decreased and apoptosis was increased by HULC knockdown. HULC knockdown arrested PC3 cells at G0/G1 phase. DU-145 was sensitive to irradiation, and resistance to irradiation of DU-145 cells was enhanced by HULC overexpression. Moreover, HULC knockdown enhanced the sensitivity of PC3 xenografts to irradiation. HULC knockdown promoted autophagy through interaction with Beclin-1 and inhibition of mTOR, resulting in increased apoptosis. HULC knockdown improved sensitivity of PCa cells to irradiation both in vivo and in vitro. HULC suppressed Beclin-1 phosphorylation, thereby reduced autophagy, involving the mTOR pathway.
Highlights
Prostate cancer (PCa), the most common cancer in men, account for approximately 26% of newly diagnosed cancer cases in 2015 in the United States [1]
After irradiation (6 Gy), survival rates of PC3 and LNCaP cells with highly upregulated in liver cancer (HULC) knockdown were significantly lower than the sh-NC groups, whereas survival rates in cells with HULC overexpression were remarkably higher than the pEX-2 group
Effects of irradiation on cell apoptosis and proliferation were enhanced by HULC knockdown in PCa cells
Summary
Prostate cancer (PCa), the most common cancer in men, account for approximately 26% of newly diagnosed cancer cases in 2015 in the United States [1]. PCa is the second leading cause of deaths related to cancer, which leads to 1–2% of deaths [2]. Radiation, and hormone therapy are widely accepted to be pillars for cancer treatment [3]. By utilizing prostate specific antigen (PSA) screening, an overwhelming majority of PCa can be diagnosed at an early stage, making radiotherapy a standard treatment modality for PCa [4,5,6]. Resistance to radiation, present in approximately 10–45% of PCa, is a crucial contributing factor, which largely influences the outcome of radiotherapy [6,7]. Considering that enhanced doses of radiation may induce side-effects on normal cells around the tumor, increasing the sensitivity of PCa cells to radiation becomes a potential therapy for PCa
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