miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/Nf-κb signaling pathway in mantle cell lymphoma

Yuan, Jingjing; Zhang, Qing; Wu, Shengsheng; Yan, Suran; Zhao, Ruihua; Sun, Yuxin; Tian, Xiaoxu; Zhou, Keshu

doi:10.1016/j.exphem.2021.08.010

Cited by 5 publications

(5 citation statements)

References 29 publications

(35 reference statements)

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“…miRNAs are small (~20-22 nucleotides) noncoding regulatory RNAs that bind to a specific target mRNA through a sequence that is complementary to the 3′-UTR of the target mRNA [23]. Several miRNAs regulate oncogenic or tumorsuppressive pathways, such as the NF-κB or BCR signaling cascade in B-cell malignancies [21,22,24,25]. Our previous studies have shown aberrant regulation of miR-377 in germinal center-type DLBCL that targets BCL-xL, and thus drives acquired resistance to BCL-xL inhibition by venetoclax [23].…”

Section: Introductionmentioning

confidence: 99%

Cooperative miRNA-dependent PTEN regulation drives resistance to BTK inhibition in B-cell lymphoid malignancies

Kapoor

Bodo²,

Hill³

et al. 2021

Cell Death Dis

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Aberrant microRNA (miR) expression plays an important role in pathogenesis of different types of cancers, including B-cell lymphoid malignancies and in the development of chemo-sensitivity or -resistance in chronic lymphocytic leukemia (CLL) as well as diffuse large B-cell lymphoma (DLBCL). Ibrutinib is a first-in class, oral, covalent Bruton’s tyrosine kinase (BTK) inhibitor (BTKi) that has shown impressive clinical activity, yet many ibrutinib-treated patients relapse or develop resistance over time. We have reported that acquired resistance to ibrutinib is associated with downregulation of tumor suppressor protein PTEN and activation of the PI3K/AKT pathway. Yet how PTEN mediates chemoresistance in B-cell malignancies is not clear. We now show that the BTKi ibrutinib and a second-generation compound, acalabrutinib downregulate miRNAs located in the 14q32 miRNA cluster region, including miR-494, miR-495, and miR-543. BTKi-resistant CLL and DLBCL cells had striking overexpression of miR-494, miR-495, miR-543, and reduced PTEN expression, indicating further regulation of the PI3K/AKT/mTOR pathway in acquired BTKi resistance. Additionally, unlike ibrutinib-sensitive CLL patient samples, those with resistance to ibrutinib treatment, demonstrated upregulation of 14q32 cluster miRNAs, including miR-494, miR-495, and miR-543 and decreased pten mRNA expression. Luciferase reporter gene assay showed that miR-494 directly targeted and suppressed PTEN expression by recognizing two conserved binding sites in the PTEN 3′-UTR, and subsequently activated AKTSer473. Importantly, overexpression of a miR-494 mimic abrogated both PTEN mRNA and protein levels, further indicating regulation of apoptosis by PTEN/AKT/mTOR. Conversely, overexpression of a miR-494 inhibitor in BTKi-resistant cells restored PTEN mRNA and protein levels, thereby sensitizing cells to BTKi-induced apoptosis. Inhibition of miR-494 and miR-495 sensitized cells by cooperative targeting of pten, with additional miRNAs in the 14q32 cluster that target pten able to contribute to its regulation. Therefore, targeting 14q32 cluster miRNAs may have therapeutic value in acquired BTK-resistant patients via regulation of the PTEN/AKT/mTOR signaling axis.

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Section: Introductionmentioning

confidence: 99%

Cooperative miRNA-dependent PTEN regulation drives resistance to BTK inhibition in B-cell lymphoid malignancies

Kapoor

Bodo²,

Hill³

et al. 2021

Cell Death Dis

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“…Chemoresistance is a major challenge resulting in cancer recurrence and an unfavorable prognosis [ 80 ]. Recent findings demonstrate that NF-κB regulates chemotherapy resistance in various tumors, including gastric cancer [ 81 , 82 ], CRC [ 83 ], NSCLC [ 84 , 85 , 86 ], pancreatic ductal adenocarcinoma (PDAC) [ 87 ], breast cancer [ 88 , 89 , 90 , 91 , 92 ], prostate cancer [ 93 ], GBM [ 94 , 95 ], and hematological tumors [ 96 , 97 , 98 , 99 ].…”

Section: Association Of Nf-κb With Therapeutic Resistancementioning

confidence: 99%

“…Mantle cell lymphoma (MCL) is a refractory aggressive lymphoma with an adverse clinical outcome. MiR-223-3p could directly inhibit conserved helix-loop-helix ubiquitous kinase (CHUK) and further decrease the expression of NF-κB, thereby reversing Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib resistance in MCL [ 96 ].…”

Section: Association Of Nf-κb With Therapeutic Resistancementioning

confidence: 99%

NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances

Sun

2023

Pharmaceuticals

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The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing therapeutic resistance. Notably, NF-κB functions as a double-edged sword exerting positive or negative influences on cancers. In this review, we summarize and discuss recent research on the regulation of NF-κB in cancer cell deaths, therapy resistance, and NF-κB-based nano delivery systems.

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“…The overexpression of miR-217 in COC1 cells facilitated CDDP-induced apoptosis and enhanced CDDP sensitivity by inhibiting the activation of the Wnt/b-catenin signaling pathway (146). In addition, multiple miRNAs, such as miR-323a-3p, miR-6727-5p, and miRNA-223-3p, have also been found to contribute to the development of cancer drug resistance by regulating apoptotic pathways via targeting other drug resistance-related signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/AKT, mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-kB) signaling pathways (147)(148)(149). Collectively, these findings indicate that targeting the apoptotic pathways is a common regulation mechanism for miRNAs in cancer drug resistance.…”

Section: Mirnas and Cancer Drug Resistance Mirnas Affect Drug-induced...mentioning

confidence: 99%

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Zhou

Jia

et al. 2022

Front. Oncol.

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Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.

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miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/Nf-κb signaling pathway in mantle cell lymphoma

Cited by 5 publications

References 29 publications

Cooperative miRNA-dependent PTEN regulation drives resistance to BTK inhibition in B-cell lymphoid malignancies

Cooperative miRNA-dependent PTEN regulation drives resistance to BTK inhibition in B-cell lymphoid malignancies

NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

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