Novel long non‐coding RNA CYB561‐5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non‐small cell lung cancer

Li, Longfei; Li, Zhimin; Qu, Jingming; Wei, Xiangju; Suo, Feng; Xu, Jilei; Liu, Xiucheng; Chang, Chen; Zheng, Shaojiang

doi:10.1111/jcmm.17057

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…Basigin is also a transmembrane protein that mainly functions in metabolic pathways, such as glycolysis, but its overexpression is associated with several pathologies including cancer [ 26 – 29 ]. In particular, its overexpression is correlated with worse overall survival in acute myeloid leukaemia, and non-small-cell lung cancer (NSCLC) and plays important role in regulation of cancer cell proliferation, invasion and metastasis [ 27 , 29 , 30 ]. Its cancer connection is mostly linked to its capacity to regulate expression/activity of monocarboxylate transporters, matrix metalloproteinases and PI3K and MAPK pathways.…”

Section: Discussionmentioning

confidence: 99%

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

et al. 2023

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Background αB-Crystallin is a heat shock chaperone protein which binds to misfolded proteins to prevent their aggregation. It is overexpressed in a wide-variety of cancers. Previous studies using human cancer cell lines and human xenograft models have suggested potential tumor promoter (oncogene) roles for αB-Crystallin in a wide-spectrum of cancers. Methods To determine the causal relationship between CRYAB overexpression and cancer, we generated a Cryab overexpression knock-in mouse model and monitor them for development of spontaneous and carcinogen (DMBA)-induced tumorigenesis. In order to investigate the mechanism of malignancies observed in this model multiple techniques were used such as immunohistochemical characterizations of tumors, bioinformatics analysis of publically available human tumor datasets, and generation of mouse embryonic fibroblasts (MEFs) for in vitro assays (clonogenic survival and migration assays and proteome analysis by mass-spectrometry). Results This model revealed that constitutive overexpression of Cryab results in the formation of a variety of lethal spontaneous primary and metastatic tumors in mice. In vivo, the overexpression of Cryab correlated with the upregulation of epithelial-to-mesenchymal (EMT) markers, angiogenesis and some oncogenic proteins including Basigin. In vitro, using E1A/Ras transformed MEFs, we observed that the overexpression of Cryab led to the promotion of cell survival via upregulation of Akt signaling and downregulation of pro-apoptotic pathway mediator JNK, with subsequent attenuation of apoptosis as assessed by cleaved caspase-3 and Annexin V staining. Conclusions Overall, through the generation and characterization of Cryab overexpression model, we provide evidence supporting the role of αB-Crystallin as an oncogene, where its upregulation is sufficient to induce tumors, promote cell survival and inhibit apoptosis.

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Section: Discussionmentioning

confidence: 99%

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

et al. 2023

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“…Basigin is also a transmembrane protein that mainly functions in metabolic pathways, such as glycolysis, but its overexpression is associated with several pathologies including cancer [19][20][21][22] . In particular, its overexpression is correlated with worse overall survival in acute myeloid leukaemia, and non-small-cell lung cancer (NSCLC) and plays important role in regulation of cancer cell proliferation, invasion and metastasis 20,22,23 . Its cancer connection is mostly linked to its capacity to regulate expression/activity of monocarboxylate transporters, matrix metalloproteinases and PI3K and MAPK pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The most signi cantly upregulated protein was Basigin, which we found had a positive correlation with the expression of Cryab, validated both in tumors compared to adjacent normal tissues and in vitro in MEFs. Basigin is also a transmembrane protein that mainly functions in metabolic pathways, such as glycolysis, but its overexpression is associated with several pathologies including cancer [19][20][21][22] . In particular, its overexpression is correlated with worse overall survival in acute myeloid leukaemia, and non-small-cell lung cancer (NSCLC) and plays important role in regulation of cancer cell proliferation, invasion and metastasis 20,22,23 .…”

Section: Discussionmentioning

confidence: 99%

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Khanna

Rashidieh²,

Bain

et al. 2022

Preprint

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αB-Crystallin is a heat shock chaperone protein which binds to misfolded proteins to prevent their aggregation. It is overexpressed in a wide-variety of cancers. Previous studies using human cancer cell lines and human xenograft models have reported tumor suppressor or tumor promoter (oncogene) roles for αB-Crystallin depending on cellular context and environmental conditions. To determine the causal relationship between CRYAB overexpression and cancer, we generated a Cryab overexpression knock-in mouse model. This model revealed that constitutive overexpression of Cryab results in the formation of a variety of lethal spontaneous primary and metastatic tumors in mice. In vivo, the overexpression of Cryab correlated with the upregulation of epithelial-to-mesenchymal (EMT) markers, angiogenesis and some oncogenic proteins including Basigin. In vitro, using E1A/Ras transformed mouse embryonic fibroblasts (MEFs), we observed that the overexpression of Cryab led to the promotion of cell survival via upregulation of Akt signaling and downregulation of pro-apoptotic pathway mediator JNK, with subsequent attenuation of apoptosis as assessed by cleaved caspase-3. Overall, through the generation and characterization of Cryab overexpression model, we provide evidence supporting the role of αB-Crystallin as an oncogene, where its upregulation is sufficient to induce tumors, promote cell survival and inhibit apoptosis.

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“…Many lncRNAs have been considered as crucial promoters or inhibitors of NSCLC progression [25], but more recently, several studies have highlighted other important roles played by lncRNAs in regulating complex cellular behaviors in NSCLC [35][36][37]. Therefore, finding novel cancerassociated lncRNAs and exploring their regulatory actions in NSCLC is necessary to identify promising targets for NSCLC treatment.…”

Section: Discussionmentioning

confidence: 99%

LncRNA PRRT3-AS1 exerts oncogenic effects on nonsmall cell lung cancer by targeting microRNA-507/homeobox B5 axis

Zhou¹,

XU²,

WANG³

et al. 2021

Oncology Research

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Long noncoding RNAs (lncRNAs) act as key regulators controlling complex cellular behaviors in nonsmall cell lung cancer (NSCLC). We investigated the expression of lncRNA PRRT3 antisense RNA 1 (PRRT3-AS1) in paired samples of NSCLC and adjacent normal tissues from a patient cohort in our hospital using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and found that it was significantly higher in NSCLC tissue than in normal tissue, consistent with The Cancer Genome Atlas database. Furthermore, functional investigation revealed that lncRNA PRRT3-AS1 depletion inhibited NSCLC-cell proliferation, colony formation, invasion, and migration, whereas its overexpression exerted the opposite effects. Moreover, PRRT3-AS1 knockdown suppressed in vivo NSCLC growth. Investigation of downstream mechanisms using RNA immunoprecipitation and luciferase reporter assay revealed that lncRNA PRRT3-AS1 acted as a competing endogenous RNA by adsorbing microRNA-507 (miR-507) and enhanced the expression of its target gene, homeobox B5 (HOXB5), in NSCLC. Furthermore, miR-507 downregulation or HOXB5 upregulation eliminated the cancer-inhibiting effects of lncRNA PRRT3-AS1 depletion in NSCLC cells. To conclude, the lncRNA PRRT3-AS1/miR-507/HOXB5 pathway acts as a promoter of malignant characteristics in NSCLC, and this newly identified competing endogenous RNA pathway may be an effective diagnostic, prognostic, and therapeutic target in NSCLC.

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Novel long non‐coding RNA CYB561‐5 promotes aerobic glycolysis and tumorigenesis by interacting with basigin in non‐small cell lung cancer

Cited by 11 publications

References 44 publications

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice

LncRNA PRRT3-AS1 exerts oncogenic effects on nonsmall cell lung cancer by targeting microRNA-507/homeobox B5 axis

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