Loss of MAP3K7 Sensitizes Prostate Cancer Cells to CDK1/2 Inhibition and DNA Damage by Disrupting Homologous Recombination

Washino, Satoshi; Rider, Leah; Romero, Lina; Jillson, Lauren K.; Affandi, Trisiani; Ohm, Angela M.; Lam, Elaine T.; Reyland, Mary E.; Costello, James C.; Cramer, Scott D.

doi:10.1158/1541-7786.mcr-18-1335

Cited by 17 publications

(14 citation statements)

References 43 publications

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“…Studies on the sensitivity of CDK1 to cancer radiotherapy have been reported previously [ 22 , 28 ]. Studies have shown that the correlation between CDK1 and radiosensitivity may be due to CDK1-mediated DNA damage and repair [ 29 , 30 ]. Here, we also determined that SNHG12 could regulate CDK1 protein level in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway

et al. 2020

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Background Radiation resistance is a major obstacle to the prognosis of cervical cancer (CC) patients. Many studies have confirmed that long non-coding RNAs (lncRNAs) are involved in the regulation of radiosensitivity of cancers. However, whether small nucleolar RNA host gene 12 (SNHG12) regulates the radiosensitivity of CC remains unknown. Methods Quantitative real-time polymerase chain reaction was used to measure the expression levels of SNHG12 and microRNA-148a (miR-148a). The radiosensitivity of cells was evaluated by clonogenic assay. Flow cytometry and caspase-3 activity assay were performed to assess the apoptosis ability and cell cycle distribution of cells. Besides, dual-luciferase reporter and RNA immunoprecipitation assay were used to verify the interaction between miR-148a and SNHG12 or cyclin-dependent kinase 1 (CDK1). Also, the protein levels of CDK1, CCND1 and γ-H2AX were detected by western blot analysis. Furthermore, in vivo experiments were conducted to verify the effect of SNHG12 on CC tumor growth. Ki-67 and TUNEL staining were employed to evaluate the proliferation and apoptosis rates in vivo. The hematoxylin and eosin (HE) staining were employed to evaluate the tumor cell morphology. Results SNHG12 was upregulated in CC tissues and cells, and its knockdown improved the radiosensitivity by promoting the radiation-induced apoptosis and cell cycle arrest of CC cells. Also, miR-148a could be sponged by SNHG12 and could target CDK1. MiR-148a inhibitor or CDK1 overexpression could invert the promotion effect of silenced-SNHG12 on CC radiosensitivity. Meanwhile, SNHG12 interference reduced the tumor growth of CC, increased miR-148a expression, and inhibited CDK1 level in vivo. Conclusion LncRNA SNHG12 promoted CDK1 expression to regulate the sensitivity of CC cells to radiation through sponging miR-148a, indicating that SNHG12 could be used as a potential biomarker to treat the radiotherapy resistance of CC patients.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway

et al. 2020

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“…MAP3K7, which is known as TAK1(TGF-β-activated kinase-1), can be rapidly activated in response to TGF-β signal transduction 26 . MAP3K7 has been reported to participate in the development of various tumors 27,28 . With the deepening of research, we found that the expression of MAP3K7 was upregulated in GC samples.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer

Hong

et al. 2020

Cell Death Dis

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Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.

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“…Alterations in DNA repair pathways and the cell cycle (Fig. 5B and C) were of particular interest as we have recently shown that loss of MAP3K7 induces sensitivity to the combination of the cell-cycle checkpoint inhibitor dinaciclib and DNA-damaging agents (46). One of the strongest negative enrichments seen in TCGA prostate cancer data was that of the G 2 -M transition (Fig.…”

Section: Loss Of Map3k7 Induced Changes In Androgen-regulated Cellcycle Progressionmentioning

confidence: 97%

MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1

Jillson

Rider

Rodrigues

et al. 2021

Molecular Cancer Research

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Prostate cancer genomic subtypes that stratify aggressive disease and inform treatment decisions at the primary stage are currently limited. Previously, we functionally validated an aggressive subtype present in 15% of prostate cancer characterized by dual deletion of MAP3K7 and CHD1. Recent studies in the field have focused on deletion of CHD1 and its role in androgen receptor (AR) chromatin distribution and resistance to AR-targeted therapy; however, CHD1 is rarely lost without codeletion of MAP3K7. Here, we show that in the clinically relevant context of co-loss of MAP3K7 and CHD1 there are significant, collective changes to aspects of AR signaling. Although CHD1 loss mainly impacts the expansion of the AR cistrome, loss of MAP3K7 drives increased AR target gene expression. Prostate cancer cell line models engineered to cosuppress MAP3K7 and CHD1 also demonstrated increased AR-v7 expression and resistance to the AR-targeting drug enzalutamide. Furthermore, we determined that low protein expression of both genes is significantly associated with biochemical recurrence (BCR) in a clinical cohort of radical prostatectomy specimens. Low MAP3K7 expression, however, was the strongest independent predictor for risk of BCR over all other tested clinicopathologic factors including CHD1 expression. Collectively, these findings illustrate the importance of MAP3K7 loss in a molecular subtype of prostate cancer that poses challenges to conventional therapeutic approaches.Implications: These findings strongly implicate MAP3K7 loss as a biomarker for aggressive prostate cancer with significant risk for recurrence that poses challenges for conventional androgen receptor-targeted therapies.

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Loss of MAP3K7 Sensitizes Prostate Cancer Cells to CDK1/2 Inhibition and DNA Damage by Disrupting Homologous Recombination

Cited by 17 publications

References 43 publications

RETRACTED ARTICLE: LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway

RETRACTED ARTICLE: LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway

Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer

MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1

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