The RNA helicase DHX33 is required for cancer cell proliferation in human glioblastoma and confers resistance to PI3K/mTOR inhibition

Wang, Hongzhong; Yu, Junyan; Wang, Xingshun; Zhang, Yandong

doi:10.1016/j.cellsig.2018.12.005

Cited by 23 publications

(16 citation statements)

References 25 publications

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“…DHX33 is highly expressed in several cancer types, including glioblastoma [ 140 ]. Knockdown in the U118-MG glioblastoma line resulted in reduced cell proliferation, cell migration, and/or reduced anchorage-independent growth [ 140 ], a result that is interesting, since it appears that DHX33 is not essential in most cell lines ( ). Overexpression of DHX33 conferred resistance to the mTOR inhibitors, rapamycin, and Torin1 [ 140 ].…”

Section: Target- or Structure-specific Helicasesmentioning

confidence: 99%

General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation

Shen

Pelletier

2020

IJMS

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DExD (DDX)- and DExH (DHX)-box RNA helicases, named after their Asp-Glu-x-Asp/His motifs, are integral to almost all RNA metabolic processes in eukaryotic cells. They play myriad roles in processes ranging from transcription and mRNA-protein complex remodeling, to RNA decay and translation. This last facet, translation, is an intricate process that involves DDX/DHX helicases and presents a regulatory node that is highly targetable. Studies aimed at better understanding this family of conserved proteins have revealed insights into their structures, catalytic mechanisms, and biological roles. They have also led to the development of chemical modulators that seek to exploit their essential roles in diseases. Herein, we review the most recent insights on several general and target-specific DDX/DHX helicases in eukaryotic translation initiation.

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Section: Target- or Structure-specific Helicasesmentioning

confidence: 99%

General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation

Shen

Pelletier

2020

IJMS

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“…Elevated expression of DHX33 was also observed in 66.3% (345/520) of hepatocellular carcinoma patients, and low DHX33 expression correlated significantly with longer survival time (12). In human glioblastoma multiforme, DHX33 is highly expressed in 84% (80/95) of cases analyzed, while 39 cases of normal cerebral tissues were all negative for DHX33 expression (13). Several oncogenic signaling pathways have been found to regulate DHX33 expression.…”

mentioning

confidence: 96%

“…Overexpression of DHX33 was found in several human cancers, such as lung, liver, lymphoma, and glioblastoma (10)(11)(12)(13). Analysis of patients with non-small-cell lung cancer indicated that DHX33 is highly expressed in 30% (28/95) of cases (11).…”

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confidence: 99%

DHX33 Interacts with AP-2β To Regulate Bcl-2 Gene Expression and Promote Cancer Cell Survival

Wang

Feng

Yuan

et al. 2019

Molecular and Cellular Biology

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The RNA helicase DHX33 has been found to be overexpressed in human cancers, where it promotes cancer development. Previous reports have shown that DHX33 deficiency caused cancer cell apoptosis, but the underlying mechanism remains unknown. In this study, we discovered that DHX33 regulates Bcl-2 family protein expression. In multiple human cancer cell lines, DHX33 was found to stimulate the transcription of Bcl-2. Mechanistically, we found that DHX33 interacts with the AP-2␤ transcription factor and acts as a coactivator to stimulate Bcl-2 gene transcription. DHX33 deficiency abolished the loading of AP-2␤ onto the promoter of Bcl-2 and thereby reduced the recruitment of active RNA polymerase II during transcription initiation. Acute knockdown of DHX33 in multiple human cancer cells caused decreased Bcl-2 protein level, which ultimately triggered mitochondrionmediated cellular apoptosis. In addition, we found that normal human lung and mammary epithelial cells were less sensitive to acute DHX33 knockdown, implying that cancer cells are uniquely responsive to DHX33 reduction. These data support the notion that disruption of DHX33 function could be an important application for cancer therapy.

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“…37 We predicted 21 candidate genes as the possible targets of miR-670-5p, of which PPP2CA, YOD1, PROX1, SEMA4B, DHX33, and SP1 were associated with tumor proliferation, migration, or invasion according to the published literature. [38][39][40][41][42][43] hsa_circ_0000337 was observed to be upregulated in ESCC in a chip-based discovery study, 8 and it was also validated in the current study by expanding the sample size. We further investigated the expression level of hsa_circ_0000337 in ESCC cell lines.…”

Section: Discussionmentioning

confidence: 65%

<p>Upregulated circ RNA hsa_circ_0000337 promotes cell proliferation, migration, and invasion of esophageal squamous cell carcinoma</p>

Song¹,

Xu²,

Shi³

et al. 2019

CMAR

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Background As a new class of endogenous ncRNAs, circRNAs have been recently verified to be involved in the carcinogenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a candidate circRNA (hsa_circ_0000337) in esophageal squamous cell carcinoma (ESCC). Patients and methods The altered expression of hsa_circ_0000337 was validated in clinical samples from 48 patients with ESCC. The human esophageal carcinoma cell lines KYSE-150 and TE-1, and the normal human esophageal epithelial cell line (HET-1A) were applied for functional analysis of hsa_circ_0000337. Cell proliferation was measured using the Cell Counting Kit-8 assay and the colony formation assay. Cell invasion and migration were detected by Transwell and wound healing assays, respectively. We further performed bioinformatic analysis and luciferase reporter assays to explore the role of hsa_circ_0000337 as a miRNA sponge. Results hsa_circ_0000337 was significantly upregulated in ESCC tissues compared to adjacent normal-appearing tissues ( P <0.0001). In our in vitro experiment, the expression of hsa_circ_0000337 was higher in TE-1 compared to the normal human esophageal epithelial cell line HET-1A ( P <0.001), but was not significantly different in KYSE-150 ( P >0.05). Knockdown of hsa_circ_0000337 significantly inhibited cell proliferation, migration, and invasion in TE-1 and KYSE-150 cell lines. Bioinformatics predicted and luciferase reporter assay verified that hsa_circ_0000337 could bind to miR-670-5p, a ncRNA involved in carcinogenesis. It is estimated that 21 genes are regulated by miR-670-5p. Conclusion hsa_circ_0000337 was found to be an upregulated circRNA that is related to ESCC and promotes the progression of disease by regulating cell proliferation, migration, and invasion. These findings suggest that this circRNA could be a promising diagnostic biomarker and potential therapeutic target.

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The RNA helicase DHX33 is required for cancer cell proliferation in human glioblastoma and confers resistance to PI3K/mTOR inhibition

Cited by 23 publications

References 25 publications

General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation

General and Target-Specific DExD/H RNA Helicases in Eukaryotic Translation Initiation

DHX33 Interacts with AP-2β To Regulate Bcl-2 Gene Expression and Promote Cancer Cell Survival

<p>Upregulated circ RNA hsa_circ_0000337 promotes cell proliferation, migration, and invasion of esophageal squamous cell carcinoma</p>

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