Kctd20 promotes the development of non‐small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients

Zhang, Xiupeng; Zhou, Haijing; Cai, Lin; Fan, Chuifeng; Liu, Yang; Wang, Liang; Li, Qingchang; Miao, Yuan

doi:10.1002/mc.22660

Cited by 9 publications

(9 citation statements)

References 18 publications

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“…However, to the best of our knowledge, the role of KCTD20 in the development and progression of other types of cancer remains unclear. Consistent with a previous report on KCTD20 in NSCLC, the present study demonstrated that KCTD20 expression was upregulated in glioma tissues compared with in normal tissues ( 63 ). The present study demonstrated that miR-324-5p may bind directly to the KCTD20 3′-UTR to regulate its expression.…”

Section: Discussionsupporting

confidence: 93%

Long non‑coding RNA NEAT1 regulates glioma cell proliferation and apoptosis by competitively binding to microRNA‑324‑5p and upregulating KCTD20 expression

Zhang

Liu

et al. 2021

Oncol Rep

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Previous studies have demonstrated that long non-coding RNAs (lncRNAs) serve a key role in the development and progression of several types of cancer, including glioma. The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) contributes to cancer growth through its effects on cell proliferation, migration, invasion and drug resistance. However, the exact regulatory mechanisms via which NEAT1 acts in glioma are unclear. In the present study, the expression levels and function of NEAT1 in glioma tissues and cell lines were examined in vitro and in vivo. By reverse transcription-quantitative PCR and fluorescence in situ hybridization analysis, NEAT1 expression was upregulated in glioma tissues compared with in adjacent normal brain tissues, and elevated NEAT1 levels were associated with poor prognosis. Cell Counting Kit-8, colony formation, ethynyldeoxyuridine, flow cytometry and western blotting assays were performed to detect the effects of NEAT1 on cell biological behavior. Knockdown of NEAT1 in glioma cell lines was associated with cell cycle arrest at the G 0 /G 1 phase, decreased proliferation and elevated apoptosis in vitro, and resulted in reduced tumor growth and increased survival in a mouse xenograft model of glioma. Using bioinformatics analysis, RNA immunoprecipitation experiments and luciferase reporter assays, it was demonstrated that NEAT1 may competitively bind to microRNA (miR)-324-5p, thus blocking its interaction with target mRNAs. Potassium channel tetramerization protein domain containing 20 (KCTD20) was identified as a specific miR-324-5p target. Accordingly, the inhibition of NEAT1 resulted in the downregulation of KCTD20 through competitive binding with miR-324-5p, decreased cell proliferation and increased apoptosis. Concomitant NEAT1 knockdown and inhibition of miR-324-5p partially reversed the effects of NEAT1 knockdown on cell proliferation and apoptosis, and further regulated KCTD20 expression. Collectively, the present findings demonstrated that NEAT1 acted as a competing endogenous RNA for miR-324-5p, and identified the NEAT1/miR-324-5p/KCTD20 axis as a novel regulatory axis and a potential therapeutic target for human glioma.

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Section: Discussionsupporting

confidence: 93%

Long non‑coding RNA NEAT1 regulates glioma cell proliferation and apoptosis by competitively binding to microRNA‑324‑5p and upregulating KCTD20 expression

Zhang

Liu

et al. 2021

Oncol Rep

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“…Further involvement of KCTD5 in other tumor types has not yet been described, but Brockmann and colleagues demonstrated that KCTD5 may switch off the Akt pathway, which regulates cell survival, cell cycle progression and cellular growth [ 112 ]. Furthermore, since the AKT pathway interplays with Hh signaling through the non-canonical pathway, it may be possible that KCTD5 alterations affect the Hh signaling-dependent tumorigenesis [ 113 , 114 ].…”

Section: Insides Into the Role Of E G H Groups And Other Kctd Proteins In Cancermentioning

confidence: 99%

The emerging role of the KCTD proteins in cancer

et al. 2021

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The human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members’ involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated.

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“…with Alzheimer's risk (GWAS) 110 Degrades RhoA 33,76 Regulates apoptosis 120 Inhibits NF-κB and AP-1 118 Aa a tumor suppressor in nonsmall cell lung cancer 121 Poor prognosis if overexpressed in breast cancer 122 Overexpressed in osteosarcoma 123 16,96 ) Inhibits mTORC1 activity 14 Inhibits Hh pathway by degrading HDAC 12 Deletion/ reduced expression in medulloblastoma 94 Loss of heterozygosity in prostate adenocarcinoma 129 Reduced expression in hepatocellular carcinoma 130 (Continues) Inhibits transcription factor AP-2α 9 and Wnt signaling by degrading β-catenin 131 I27N mutation caused kidney dysfunction in mice 132 Missense mutations associated with scalp-ear-nipple syndrome 133 Other Regulates GABA B2 signaling 17,135,136 ND Other KCNRG ND Kv channel 139,140 Suppresses K + channel activity 139 Deleted in B-cell chronic lymphocytic leukemia, [140][141][142] prostate cancer 140 and multiple myeloma 142 Other KCTD18 ND ND ND Duplication of 2q33 in one patient with epilepsy, devel. delay, autistic behavior 143 Haplotype associated with restless legs syndrome 144 G KCTD20 ND ND Activates Akt 145,146 Gen var associated with insulin resistance (GWAS) 147 BTBD10 ND Akt1-3 148 Inhibits apoptosis, activates Akt 149,150 Sporadic amyotrophic lateral sclerosis 151…”

Section: Figurementioning

confidence: 99%

KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders

et al. 2019

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The underlying molecular basis for neurodevelopmental or neuropsychiatric disorders is not known. In contrast, mechanistic understanding of other brain disorders including neurodegeneration has advanced considerably. Yet, these do not approach the knowledge accrued for many cancers with precision therapeutics acting on well‐characterized targets. Although the identification of genes responsible for neurodevelopmental and neuropsychiatric disorders remains a major obstacle, the few causally associated genes are ripe for discovery by focusing efforts to dissect their mechanisms. Here, we make a case for delving into mechanisms of the poorly characterized human KCTD gene family. Varying levels of evidence support their roles in neurocognitive disorders ( KCTD3 ), neurodevelopmental disease ( KCTD7 ), bipolar disorder ( KCTD12 ), autism and schizophrenia ( KCTD13 ), movement disorders ( KCTD17 ), cancer ( KCTD11 ), and obesity ( KCTD15 ). Collective knowledge about these genes adds enhanced value, and critical insights into potential disease mechanisms have come from unexpected sources. Translation of basic research on the KCTD‐related yeast protein Whi2 has revealed roles in nutrient signaling to mTORC1 (KCTD11) and an autophagy‐lysosome pathway affecting mitochondria (KCTD7). Recent biochemical and structure‐based studies (KCTD12, KCTD13, KCTD16) reveal mechanisms of regulating membrane channel activities through modulation of distinct GTPases. We explore how these seemingly varied functions may be disease related.

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Kctd20 promotes the development of non‐small cell lung cancer through activating Fak/AKT pathway and predicts poor overall survival of patients

Cited by 9 publications

References 18 publications

Long non‑coding RNA NEAT1 regulates glioma cell proliferation and apoptosis by competitively binding to microRNA‑324‑5p and upregulating KCTD20 expression

Long non‑coding RNA NEAT1 regulates glioma cell proliferation and apoptosis by competitively binding to microRNA‑324‑5p and upregulating KCTD20 expression

The emerging role of the KCTD proteins in cancer

KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders

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