miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential

Meyer, Sara E.; Muench, David E.; Rogers, Andrew M.; Newkold, Tess; Orr, Emily; O’Brien, Eric; Perentesis, John P.; Doench, John G.; Lal, Ashish; Morris, Patrick J.; Thomas, Craig J.; Lieberman, Judy; McGlinn, Edwina; Aronow, Bruce J.; Salomonis, Nathan; Grimes, H. Leighton

doi:10.1084/jem.20171312

Cited by 24 publications

(23 citation statements)

References 118 publications

(189 reference statements)

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“…Based on the previous report, Cdkn1b (p27 Kip1 ), known as the tumor-suppressive protein, could be the target of miR-196b. 9 After the miR-196b mimic., we first checked the Cdkn1b expression by PCR and found that Cdkn1b expression was significantly decreased. Besides, the protein level of Cdkn1b was found to be reduced after miR-196b overexpression, as presented in Figure 3A and B.…”

Section: Cdkn1b As the Target Modulated By Mir-196bmentioning

confidence: 99%

<p>High Expression of miR-196b Predicts Poor Prognosis in Patients with Ovarian Cancer</p>

Li¹,

Li²,

Liu³

et al. 2020

OTT

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Background/Aims: To analyze the clinical significance of miR-196b expression in ovarian cancer and predict the function and possible mechanism of miR-196b. Methods: Both Kaplan-Meier (K-M) and Cox proportional hazards regression model were used to analyze the prognostic factors of patients with ovarian cancer. MiR196-b was modulated in ovarian cancer cells, and the cell viability, cell cycle, and cell cycle-related gene expression were analyzed. The target genes of miR-196b were then predicted and checked the relationship between the target genes. Results: MiR-196b was an independent risk factor, while high expression of miR-196b was associated with poor prognosis of ovarian cancer. MiR-196b overexpression increased cancer cell proliferation. Cdkn1b, as one of the targets of miR-196b, was related to cell viability and mitosis. Conclusion: High expression of miR-196b was significantly associated with poor prognosis of the patients with ovarian cancer. MiR-196b could increase the cell proliferation of ovarian cancer by modulating Cdkn1b expression.

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Section: Cdkn1b As the Target Modulated By Mir-196bmentioning

confidence: 99%

<p>High Expression of miR-196b Predicts Poor Prognosis in Patients with Ovarian Cancer</p>

Li¹,

Li²,

Liu³

et al. 2020

OTT

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“…Numerous miRNAs function as oncogenes or tumor suppressors in most cancers, depending on the cancer tissue type (29). miR-196b-5p functions in cancer pathogenesis in a context-dependent manner (30)(31)(32)(33) but remains controversial in lung cancer. Recent reports indicate that miR-196b-5p inhibits lung cancer progression and metastasis by targeting LIN28 and Runx2 (33,34).…”

Section: Qki-5 Interacts With Mir-196b-5p and Negatively Regulates Itsmentioning

confidence: 99%

miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer

Liang

Wang

Huang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

128

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Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

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“…The discovery of multiple targets of miRNA raises the question of which ones are direct targets of a certain miRNA, especially in regard to non-canonical binding in specific cellular contexts, such as chromosomal translocation. By combining miRNA mimic pull-down and shRNA functional screening, a recent study claimed that Cdkn1b ( p27Kip1 ) was a genuine target of miR-196 in the specific MLL -rearranged context (Meyer et al, 2018). In addition to their cell-intrinsic functions, miRNAs exert their roles in a non-cell intrinsic manner; for example, miR-125b induces VEGFA production in MLL–AF9-driven leukemia (Liu et al, 2017).…”

Section: The Multifaceted Functions Of Ncrnas In Fusion Protein-drivementioning

confidence: 99%

Non-coding RNAs in cancers with chromosomal rearrangements: the signatures, causes, functions and implications

Han

Sun

Wang

et al. 2019

Journal of Molecular Cell Biology

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Chromosomal translocation leads to the juxtaposition of two otherwise separate DNA loci, which could result in gene fusion. These rearrangements at the DNA level are catastrophic events and often have causal roles in tumorigenesis. The oncogenic DNA messages are transferred to RNA molecules, which are in most cases translated into cancerous fusion proteins. Gene expression programs and signaling pathways are altered in these cytogenetically abnormal contexts. Notably, non-coding RNAs have attracted increasing attention and are believed to be tightly associated with chromosome-rearranged cancers. These RNAs not only function as modulators in downstream pathways but also directly affect chromosomal translocation or the associated products. This review summarizes recent research advances on the relationship between non-coding RNAs and chromosomal translocations and on diverse functions of non-coding RNAs in cancers with chromosomal rearrangements.

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miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential

Cited by 24 publications

References 118 publications

<p>High Expression of miR-196b Predicts Poor Prognosis in Patients with Ovarian Cancer</p>

<p>High Expression of miR-196b Predicts Poor Prognosis in Patients with Ovarian Cancer</p>

miR-196b-5p–mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer

Non-coding RNAs in cancers with chromosomal rearrangements: the signatures, causes, functions and implications

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