miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B

Zhang, Li; Zeng, Daxiong; Chen, Ying; Li, Ning; Lv, Yantian; Yong, Li; Xu, Xiao; Xu, Guo

doi:10.1016/j.lfs.2016.05.014

Cited by 28 publications

(22 citation statements)

References 23 publications

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“…Cancer-associated genes were obtained from the Catalogue of Somatic Mutations in Cancer [31] database. Previous studies supported our results that most of the 22 SCNA-miRNA except for four miRNAs (hsa-mir-1976, hsa-mir-3913-1, hsa-mir-3615, and hsa-mir-1306) are related to cancer development [32,33,34,35,36,37,38,39]. However, few relationships were identified between miRNAs and co-located cancer-associated genes except for in the chr9p21.3 locus.…”

Section: Resultssupporting

confidence: 91%

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Soh

Cho

Choi

et al. 2018

Cancers

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MicroRNAs (miRNAs) are key molecules that regulate biological processes such as cell proliferation, differentiation, and apoptosis in cancer. Somatic copy number alterations (SCNAs) are common genetic mutations that play essential roles in cancer development. Here, we investigated the association between miRNAs and SCNAs in cancer. We collected 2538 tumor samples for seven cancer types from The Cancer Genome Atlas. We found that 32−84% of miRNAs are in SCNA regions, with the rate depending on the cancer type. In these regions, we identified 80 SCNA-miRNAs whose expression was mainly associated with SCNAs in at least one cancer type and showed that these SCNA-miRNAs are related to cancer by survival analysis and literature searching. We also identified 58 SCNA-miRNAs common in the seven cancer types (CC-SCNA-miRNAs) and showed that these CC-SCNA-miRNAs are more likely to be related with protein and gene expression than other miRNAs. Furthermore, we experimentally validated the oncogenic role of miR-589. In conclusion, our results suggest that SCNA-miRNAs significantly alter biological processes related to cancer development, confirming the importance of SCNAs in non-coding regions in cancer.

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Section: Resultssupporting

confidence: 91%

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Soh

Cho

Choi

et al. 2018

Cancers

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“…Specifically, while Zhang et al . demonstrated that INPP4B suppresses proliferation, colony formation potential and anchorage-independent growth in lung cancer [ 24 ], our clinical findings indicate high levels of INPP4B expression are associated with poor patient outcome. It is important to note however, that only bladder cancer is part of the four cancers which met subsequent FDR 10-90% <0.05 cut-off, and are hence high confidence hits.…”

Section: Discussionmentioning

confidence: 67%

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML

et al. 2018

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Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher’s exact P values). In our study, Fisher’s exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B’s prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

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“…Therefore, INPP4B mediated PtdIns(3)P generation may contribute to the activation of SGK3. SGK3 has been reported to mediate the oncogenic role of INPP4B in many cancers, including lung cancer, breast cancer and melanoma (6,12,13). In either melanoma cell lines or fresh melanoma isolates with various levels of INPP4B, the phosphorylation levels of SGK3 are positively correlated with the expressing levels of INPP4B.…”

Section: Discussionmentioning

confidence: 99%

“…INPP4B was initially characterized as an inositol polyphosphate phosphatase hydrolyzing PtdIns (3,4)P2 to PtdIns(3)P. As the intracellular PI (3,4)P2 is required for the full activation of Akt, a critical oncogene in various cancers, INPP4B can restrain the PI3K/Akt signaling (5). Recently, INPP4B was shown to play a tumor suppressor role in variety of cancers, including lung, prostate, bladder and melanocytic cancers (6)(7)(8)(9). The tumor suppressive mechanism of INPP4B has been attributed to its negative regulation role in PI3K/Akt signaling.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-605 functions as a tumor suppressor by targeting INPP4B in melanoma

et al. 2017

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MicroRNAs (miRNAs) play crucial roles in the initiation and progression of various cancers, including melanoma. Recently, the genetic variants and deregulation of miR-605 have been reported to participate in carcinogenesis. However, the expression status of the miR-605 in melanoma tissues and its role in melanoma progression remain unknown. In this study, we found that miR-605 was significantly downregulated in melanoma cell lines and clinical specimens. Further function studies demonstrated that miR-605 suppressed melanoma cell growth both in vitro and in vivo. Moreover, INPP4B gene was identified as a target of miR-605 through bioinformatics analysis and luciferase reporter assays. Further analysis demonstrated that the inhibition of INPP4B mediated SGK3 activation was required for the suppressive role of miR-605 on melanomas cell growth. Collectively, our data suggest that miR-605 functions as a tumor suppressor by negatively regulating INPP4B mediated SGK3 activation in melanoma and may present a potential target for therapeutic intervention.

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miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B

Cited by 28 publications

References 23 publications

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML

MicroRNA-605 functions as a tumor suppressor by targeting INPP4B in melanoma

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