Shaoxi Niu

Abstract Aberrant N6-methyladenosine (m6A) modification has emerged as a driver of tumor initiation and progression, yet how long noncoding RNAs (lncRNA) are involved in the regulation of m6A remains unknown. Here we utilize data from 12 cancer types from The Cancer Genome Atlas to comprehensively map lncRNAs that are potentially deregulated by DNA methylation. A novel DNA methylation–deregulated and RNA m6A reader–cooperating lncRNA (DMDRMR) facilitated tumor growth and metastasis in clear cell renal cell carcinoma (ccRCC). Mechanistically, DMDRMR bound insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) to stabilize target genes, including the cell-cycle kinase CDK4 and three extracellular matrix components (COL6A1, LAMA5, and FN1), by specifically enhancing IGF2BP3 activity on them in an m6A-dependent manner. Consequently, DMDRMR and IGF2BP3 enhanced the G1–S transition, thus promoting cell proliferation in ccRCC. In patients with ccRCC, high coexpression of DMDRMR and IGF2BP3 was associated with poor outcomes. Our findings reveal that DMDRMR cooperates with IGF2BP3 to regulate target genes in an m6A-dependent manner and may represent a potential diagnostic, prognostic, and therapeutic target in ccRCC. Significance: This study demonstrates that the lncRNA DMDRMR acts as a cofactor for IGF2BP3 to stabilize target genes in an m6A-dependent manner, thus exerting essential oncogenic roles in ccRCC.

10.1158/0008-5472.can-20-1619

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Figure S2 from Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and Neuroendocrine Differentiation by Activated ZBTB46

Yen‐Nien Liu Shaoxi Niu Wei‐Yu Chen Qingfu Zhang Yulei Tao

Supplementary Figure S2

Neuroendocrine differentiation

10.1158/1078-0432.22470728.v1

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Data from Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and Neuroendocrine Differentiation by Activated ZBTB46

Yen‐Nien Liu Shaoxi Niu Weiyu Chen Qingfu Zhang Yulei Tao

<div>AbstractPurpose:The molecular targets for castration-resistant prostate cancer (CRPC) are unknown because the disease inevitably recurs, and therapeutic approaches for patients with CRPC remain less well understood. We sought to investigate regulatory mechanisms that result in increased therapeutic resistance, which is associated with neuroendocrine differentiation of prostate cancer and linked to dysregulation of the androgen-responsive pathway.Experimental Design:The underlying intracellular mechanism that sustains the oncogenic network involved in neuroendocrine differentiation and therapeutic resistance of prostate cancer was evaluated to investigate and identify effectors. Multiple sets of samples with prostate adenocarcinomas and CRPC were assessed via IHC and other assays.Results:We demonstrated that leukemia inhibitory factor (LIF) was induced by androgen deprivation therapy (ADT) and was upregulated by ZBTB46 in prostate cancer to promote CRPC and neuroendocrine differentiation. LIF was found to be induced in patients with prostate cancer after ADT and was associated with enriched nuclear ZBTB46 staining in high-grade prostate tumors. In prostate cancer cells, high ZBTB46 output was responsible for the activation of LIF-STAT3 signaling and neuroendocrine-like features. The abundance of LIF was mediated by ADT-induced ZBTB46 through a physical interaction with the regulatory sequence of LIF. Analysis of serum from patients showed that cases of higher tumor grade and metastatic prostate cancer exhibited higher LIF titers.Conclusions:Our findings suggest that LIF is a potent serum biomarker for diagnosing advanced prostate cancer and that targeting the ZBTB46–LIF axis may therefore inhibit CRPC development and neuroendocrine differentiation after ADT.</div>

Neuroendocrine differentiation

10.1158/1078-0432.c.6527663.v1

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Data from Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and Neuroendocrine Differentiation by Activated ZBTB46

Yen‐Nien Liu Shaoxi Niu Weiyu Chen Qingfu Zhang Yulei Tao

<div>AbstractPurpose:The molecular targets for castration-resistant prostate cancer (CRPC) are unknown because the disease inevitably recurs, and therapeutic approaches for patients with CRPC remain less well understood. We sought to investigate regulatory mechanisms that result in increased therapeutic resistance, which is associated with neuroendocrine differentiation of prostate cancer and linked to dysregulation of the androgen-responsive pathway.Experimental Design:The underlying intracellular mechanism that sustains the oncogenic network involved in neuroendocrine differentiation and therapeutic resistance of prostate cancer was evaluated to investigate and identify effectors. Multiple sets of samples with prostate adenocarcinomas and CRPC were assessed via IHC and other assays.Results:We demonstrated that leukemia inhibitory factor (LIF) was induced by androgen deprivation therapy (ADT) and was upregulated by ZBTB46 in prostate cancer to promote CRPC and neuroendocrine differentiation. LIF was found to be induced in patients with prostate cancer after ADT and was associated with enriched nuclear ZBTB46 staining in high-grade prostate tumors. In prostate cancer cells, high ZBTB46 output was responsible for the activation of LIF-STAT3 signaling and neuroendocrine-like features. The abundance of LIF was mediated by ADT-induced ZBTB46 through a physical interaction with the regulatory sequence of LIF. Analysis of serum from patients showed that cases of higher tumor grade and metastatic prostate cancer exhibited higher LIF titers.Conclusions:Our findings suggest that LIF is a potent serum biomarker for diagnosing advanced prostate cancer and that targeting the ZBTB46–LIF axis may therefore inhibit CRPC development and neuroendocrine differentiation after ADT.</div>

Neuroendocrine differentiation

10.1158/1078-0432.c.6527663

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Additional file 1 of Genomic profiling of Chinese patients with urothelial carcinoma

Figshare (2021)

Bo Yang Xiao Zhao Chong Wan Xin Ma Shaoxi Niu

Additional file 1.

Profiling (computer programming)

10.6084/m9.figshare.14037337

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