Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2

Xu, Lei; Zhang, Bin; Li, Wenlan

doi:10.3892/mmr.2021.11902

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…We found that PUM2 exhibited higher activity in ovarian cancer cells (Fig. 2F), and targeting PUM2 has been identi ed as an effective way to reverse cisplatin resistance in OvC 21 . HNRNPDL exhibited higher activity in T cells of lung cancer (Fig.…”

Section: Rbp Regulators Exhibit Cancer and Cell Speci Citymentioning

confidence: 81%

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

Zhou

Jie

et al. 2022

Preprint

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RNA-binding proteins (RBPs) are key players of gene expression and perturbation of RBP-RNA regulatory network has been observed in various cancer types. Here, we propose a computational method, RBPreg, to identify the RBP regulators by integration of single cell RNA-Seq (N = 233,591) and RBP binding data. Pan-cancer analyses suggest that RBP regulators exhibit cancer and cell specificity and perturbation of RBP regulatory network is involved in cancer hallmark-related functions. We prioritize an oncogenic RBP-HNRNPK, which is highly expressed in tumors and associated with poor prognosis of patients. Functional assays performed in cancer cells reveal that HNRNPK promotes cancer cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic investigations further demonstrate that HNRNPK promotes tumorigenesis and progression by directly binding to MYC and perturbed the MYC targets pathway in lung cancer. Our results provide a valuable resource for characterizing RBP regulatory networks in cancer, yielding potential biomarkers for precision medicine.

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Section: Rbp Regulators Exhibit Cancer and Cell Speci Citymentioning

confidence: 81%

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

Zhou

Jie

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…PUM2 exhibited higher activity in ovarian cancer cells (Fig. 2f ), and targeting PUM2 has been identified as an effective way to reverse cisplatin resistance in OvC 23 . HNRNPDL exhibited higher activity in T cells of lung cancer (Fig.…”

Section: Resultsmentioning

confidence: 98%

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

et al. 2023

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) are key players of gene expression and perturbations of RBP-RNA regulatory network have been observed in various cancer types. Here, we propose a computational method, RBPreg, to identify the RBP regulators by integration of single cell RNA-Seq (N = 233,591) and RBP binding data. Pan-cancer analyses suggest that RBP regulators exhibit cancer and cell specificity and perturbations of RBP regulatory network are involved in cancer hallmark-related functions. We prioritize an oncogenic RBP-HNRNPK, which is highly expressed in tumors and associated with poor prognosis of patients. Functional assays performed in cancer cells reveal that HNRNPK promotes cancer cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic investigations further demonstrate that HNRNPK promotes tumorigenesis and progression by directly binding to MYC and perturbed the MYC targets pathway in lung cancer. Our results provide a valuable resource for characterizing RBP regulatory networks in cancer, yielding potential biomarkers for precision medicine.

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“…Map2k6 played an important role in modulating I/R-induced neuron cell apoptosis [ 27 ]. PUM2 was validated to be involved in the development of ovarian cancer [ 10 ], acute ischemic kidney injury [ 11 ] and mature neurons [ 12 ]. Nonetheless, whether PUM2 is involved in cerebral I/R injury still needs to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…PUM2 is a member of the PUM family, which has been reported to participate in the progression of several diseases. For instance, PUM2 modulates the resistance to cisplatin in ovarian cancer via regulating USP46 expression [ 10 ]. PUM2 governs mitochondrial quality in acute ischemic kidney injury through cooperating with Mff [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

PUM2 aggravates the neuroinflammation and brain damage induced by ischemia–reperfusion through the SLC7A11-dependent inhibition of ferroptosis via suppressing the SIRT1

Liu

et al. 2022

Mol Cell Biochem

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Cerebral ischemia–reperfusion (I/R) injury occurs due to the restoration of blood perfusion after cerebral ischemia, which results in the damage of the brain structures and functions. Unfortunately, currently there are no effective methods for preventing and treating it. The pumilio 2 (PUM2) is a type of RBPs that has been reported to participate in the progression of several diseases. Ferroptosis is reported to be involved in I/R injury. Whether PUM2 modulated I/R injury through regulating ferroptosis remains to be elucidated. The cerebral I/R models including animal middle cerebral artery occlusion/reperfusion (MCAO/R) model and oxygen–glucose deprivation/reperfusion (OGD/R)-induced cortical neuron injury cell model of were established and, respectively. RT-qPCR was applied for evaluating PUM2, SIRT1 and SLC7A11 expression. Western blot was employed for measuring the protein expression levels. The viability of cortical neurons was tested by MTT assay. The histological damage of the brain tissues was assessed by H&E staining. The level of PUM2 was boosted in both the brain tissues of the MCAO model and OGD/R-induced cortical neuron injury model. Silence of PUM2 alleviated MCAO-induced brain injury and decreased the death of PC12 cell exposed to OGD/R. PUM2 also aggravated the accumulation of free iron in MCAO mice and OGD/R-induced cortical neuron injury model. In addition, PUM2 suppressed SLC7A11 via inhibiting expression of SIRT1. Rescue assays unveiled that downregulation of SLC7A11 reversed PUM2 mediated neuroinflammation and brain damage induced by I/R. PUM2 aggravated I/R-induced neuroinflammation and brain damage through the SLC7A11-dependent inhibition of ferroptosis by suppressing SIRT1, highlighting the role of PUM2 in preventing or treating cerebral I/R injury.

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Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2

Cited by 10 publications

References 38 publications

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer

PUM2 aggravates the neuroinflammation and brain damage induced by ischemia–reperfusion through the SLC7A11-dependent inhibition of ferroptosis via suppressing the SIRT1

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