Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis

Su, Yanhong; Meador, Jarah A.; Calaf, Gloria M.; Proietti-De-Santis, Luca; Zhao, Yongliang; Bohr, Vilhelm A.; Balajee, Adayabalam S.

doi:10.1158/0008-5472.can-10-1743

Cited by 54 publications

(65 citation statements)

References 41 publications

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“…Although aberrant expression of RECQL4 has been reported in sporadic osteoblastoma (19), breast and prostate cancer cells and tissues (20,21), its prognostic and chemotherapeutic significance in gastric cancer are not known. In this study, we demonstrated RECQL4 expression is aberrantly elevated frequently in both clinical gastric cancer samples and tumor cell lines, and a higher RECQL4 expression renders the gastric cancer cells more resistance to cisplatin treatment.…”

Section: Introductionmentioning

confidence: 99%

Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway

Fang

Niu

et al. 2016

Cancer Research

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Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic and chemotherapeutic significance of RECQL4 in human gastric cancer, which has yet to be determined. We observed significant increases in RECQL4 mRNA or protein in >70% of three independent sets of human gastric cancer specimens examined, relative to normal gastric tissues. Strikingly, high RECQL4 expression in primary tumors correlated well with poor survival and gastric cancer lines with high RECQL4 expression displayed increased resistance to cisplatin treatment. Mechanistic investigations revealed a novel role for RECQL4 in transcriptional regulation of the multidrug resistance gene MDR1, through a physical interaction with the transcription factor YB1. Notably, ectopic expression of RECQL4 in cisplatin-sensitive gastric cancer cells with low endogenous RECQL4 was sufficient to render them resistant to cisplatin, in a manner associated with YB1 elevation and MDR1 activation. Conversely, RECQL4 silencing in cisplatinresistant gastric cancer cells with high endogenous RECQL4 suppressed YB1 phosphorylation, reduced MDR1 expression, and resensitized cells to cisplatin. In establishing RECQL4 as a critical mediator of cisplatin resistance in gastric cancer cells, our findings provide a therapeutic rationale to target RECQL4 or the downstream AKT-YB1-MDR1 axis to improve gastric cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway

Fang

Niu

et al. 2016

Cancer Research

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“…For example, Fang et al (13) found that overexpression of RecQL4 due to gene amplification plays a critical role in human breast tumor progression, and Arora et al (22) demonstrated that shRNA-mediated RECQL4 suppression in MDA-MB453 breast cancer cells significantly inhibited in vitro clonogenic survival and in vivo tumorigenicity. Su et al (15) found that elevation of RECQL4 level was positively associated with the aggressiveness of prostate cancer both in vitro and in vivo, implying that RECQL4 plays critical roles in prostate-cancer carcinogenesis and is a valuable biomarker for this cancer. However, the expression level of RECQL4 in GC, and its prognostic significance remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of the RECQL4 gene are associated with the rare type II Rothmund-Thomson syndrome, which has a propensity for osteosarcomas (11,12). Recent studies have shown that RECQL4 acts as a tumor-promotor in some cancers, such as osteosarcomas, prostate cancer, colorectal cancer, and breast cancer (13)(14)(15)(16)(17). Moreover, depletion of RECQL4 has been shown to significantly reduce the proliferation of cancer cells, promote apoptosis, and impair tumorgenicity in tumor-bearing mice (13,15).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that RECQL4 acts as a tumor-promotor in some cancers, such as osteosarcomas, prostate cancer, colorectal cancer, and breast cancer (13)(14)(15)(16)(17). Moreover, depletion of RECQL4 has been shown to significantly reduce the proliferation of cancer cells, promote apoptosis, and impair tumorgenicity in tumor-bearing mice (13,15). However, the expression of RECQL4 in GC and its clinical and prognostic significance have been rarely mentioned.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of RECQL4 is associated with poor prognosis in patients with gastric cancer

et al. 2018

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Abstract. The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P<0.05) and that patients with increased RECQL4 mRNA expression levels had significantly lower overall survival (OS) (P<0.001). The results of IHC showed that the positive rate of RECQL4 in the GC samples was significantly higher than that in the normal gastric mucosa specimens (P<0.05). RECQL4 expression was positively associated with depth of invasion and TNM (P<0.05). High RECQL4 expression in GC samples was significantly associated with poor OS (P=0.024). Positive RECQL4 expression, depth of invasion, lymphatic invasion, and TNM staging were independent factors for predicting worse OS rates by using multivariate analysis. Compared with expression levels in normal gastric tissues, RECQL4 was significantly overexpressed in GC samples, and increased RECQL4 expression was an independent predictor of poor prognosis in GC patients.

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“…Recent studies show that RECQL4 expression is also increased in metastatic prostate cancer cell lines [48] as well as in sporadic osteoblastomas [49]. Loss of RECQL4 activity leads to an accumulation of double-strand breaks, and knockdown of RECQL4 decreases both tumorigenicity and invasiveness [48].…”

Section: Discussionmentioning

confidence: 99%

Altered RecQ Helicase Expression in Sporadic Primary Colorectal Cancers

Lao

Carter

Dzieciatkowski

et al. 2013

Journal of Surgical Research

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Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.

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Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis

Cited by 54 publications

References 41 publications

Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway

Human Helicase RECQL4 Drives Cisplatin Resistance in Gastric Cancer by Activating an AKT–YB1–MDR1 Signaling Pathway

Overexpression of RECQL4 is associated with poor prognosis in patients with gastric cancer

Altered RecQ Helicase Expression in Sporadic Primary Colorectal Cancers

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