RecQ helicase BLM regulates prostate cancer cell proliferation and apoptosis

Abstract

Prostate cancer (PCa) is a common malignant tumor and the second leading cause of morbidity and mortality in men worldwide. Considering the prevalence and effects of PCa in males, an understanding of the molecular mechanisms underlying PCa tumorigenesis are essential and may provide novel therapeutic strategies for treating PCa. Bloom syndrome protein (BLM) is a member of the RecQ helicase family. The major function of BLM is to uncoil the double-stranded DNA structure. It has previously been demonstrated that BLM acts as a ‘genome caretaker’, and dysregulation of BLM function has been implicated in the development of multiple tumor types; however, its potential for inducing PCa tumorigenesis remains undetermined. The present study aimed to explore the function of BLM in PCa progression. Reverse transcription-polymerase chain reaction, immunohistochemistry and western blot analyses were performed to detect the BLM expression pattern in PCa patients and cell lines. The proliferation, and migration and invasion capacities of prostate cells were determined by EdU and Transwell assays following transfection with BLM-targeting short hairpin RNA (shRNA). The expression of BLM was significantly increased in PCa tissues and PC3 cells compared with non-PCa tissues and benign prostatic hyperplasia cells. Knockdown of BLM via shRNA inhibited PCa cell proliferation, and promoted PCa cell apoptosis. Notably, reducing the expression of BLM had no effect on the migration or invasive abilities of PCa cells. These results suggest that downregulation of BLM may alleviate PCa development, providing a novel perspective for PCa tumorigenesis and a potential therapeutic target for PCa.

Distinct prognosis of mRNA expression of the five RecQ DNA-helicase family members &ndash; <em>RECQL</em>, <em>BLM</em>, <em>WRN</em>, <em>RECQL4</em>, and <em>RECQL5 </em>&ndash; in patients with breast cancer

“…BLM is overexpressed in some tumor cells, and abnormalities in BLM are associated with genome instability, which has been shown in recent studies to lead to tumorigenesis 11–13. Recently, Qian et al showed that BLM was overexpressed in prostate cancer cells and tissue compared with benign prostatic hyperplasia cells and nonprostate cancer tissue 37. In 2015, Arora et al showed that in breast cancer, overexpression of BLM mRNA was significantly correlated with increased histopathological grade, larger tumors, ER-negative tumors, PR-negative tumors, and triple-negative tumor phenotypes, and associated with reduced BCSS 38.…”

A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

“…From the pathway and interaction network analyses, we inferred that BRCA2 and BRCA1 have a majority of interacting partners that are largely associated with either DNA repair genes or helicases, viz., KRIT1, CTNS, USH2A, HEXB, MCCC1, MYO15A, CAPN3, GNPTAB, RHAG, PRLR, OTOF, GJB6, MCM8, CYP1B1, PRICKLE1, TP53, COL6A1, DNAAF1, SCN9A, CYP11B2, ATP6V0A2, NF1, ADA, MT-CYB, OPA1, ANG, HBB, MRE11 ( Figure 2B ). Notable among them is RecQ/BLM helicase, which has been recently reported to regulate cancer cell proliferation ( Qian et al, 2017 ). In the recent past, recommendations demonstrated the role of prostate serum antigen (PSA) levels correlating the patient’s race, age, and prostate volume ( Wu et al, 2017 ).…”

miR‑27b‑3p and miR‑607 cooperatively regulate BLM gene expression by directly targeting the 3'‑UTR in PC3 cells

“…Nowadays, conventional drugs such as cis-platinum and mitomycin are usually selected for use as auxiliaries in chemotherapy or radiotherapy for prostate carcinoma treatment (2,3). Several studies have directly or indirectly implied that patients with terminal cancer could be treated in the future using drugs targeting critical endogenous factors such as Her2/Neu, epidermal growth factor or tumor necrosis factor-α (2–5). Improved target selection of anti-cancer drugs is very important for clinical research.…”

“…BLM gene defects can cause Bloom syndrome, accompanied by cancer predisposition (6–9). A recent study indicated that knockdown of BLM impairs the normal proliferation and metabolism of cancer cells (5). Drugs targeting BLM have been used to treat cancer (5,10–14).…”

“…A recent study indicated that knockdown of BLM impairs the normal proliferation and metabolism of cancer cells (5). Drugs targeting BLM have been used to treat cancer (5,10–14). However, the majority of anti-cancer drugs are ineffective due to poor target specificity, and certain regulation mechanisms, such as the post-transcriptional control pathway of BLM gene expression, remain unclear, which limits the application of drugs targeting BLM for carcinoma therapy in the future.…”