Genomic and GeneChip expression profiling reveals the inhibitory effects of Amorphophalli Rhizoma in TNBC cells

Wu, Chun-Yu; Chen, Mingcang; Zhang, Qiuhua; Yu, Linghong; Zhu, Jiayan; Gao, Xiufei

doi:10.1016/j.jep.2019.02.004

Cited by 18 publications

(32 citation statements)

References 41 publications

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“…Intriguingly, the tumorigenic function of OLFML2A is also gradually emerging. The expression of OLFML2A was negatively correlated with the biological progression and clinical features of TNBC, LIHC and leukemia [10][11][12]. Moreover, as previously reported, the Wnt/β-catenin pathway is a potential regulatory target of OLFML2A, through which OLFML2A regulates several malignant biological processes in LIHC [12].…”

Section: Discussionsupporting

confidence: 74%

OLFML2A Downregulation Inhibits Glioma Proliferation through Suppression of Wnt/β-catenin Signaling

Duan

Dong

et al. 2020

Preprint

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Background: Glioma is a highly heterogeneous and lethal tumor with extremely poor prognosis. Through analysis of TCGA data, we found that OLFML2A was significantly upregulated in glioma tissues and positively correlated with glioma grade and worse prognosis. However, the molecular function of OLFML2A and its underlying mechanism in glioma remain unclear.Methods: The expression of OLFML2A in glioma was determined by immunohistochemistry (IHC). Celigo assay, MTT assay and flow cytometry were utilized to evaluate the effects of OLFML2A on glioma proliferation and apoptosis. Gene chip microarray analysis and ingenuity pathway analysis were used to investigate the potential regulatory mechanisms of OLFML2A, which were further assessed by q-PCR, western blotting and IHC. An animal transplanting glioma model and spectral computed tomography scan were used to verify OLFML2A expression in vivo.Results: In this study, we found that the expression of OLFML2A was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan-Meier survival analysis of TCGA data revealed that glioma patients with higher expression of OLFML2A had shorter overall survival. Importantly, when we knocked down the expression of OLFML2A in glioma cells, cell proliferation was inhibited, and apoptosis was promoted. Mechanistically, downregulation of OLFML2A inhibited Wnt/β-catenin signaling by directly reducing the level of stabilized β-catenin and upregulating the expression of amyloid precursor protein (APP) to indirectly suppress β-catenin, leading to repression of MYC, CD44 and CSKN2A2 expression. Furthermore, we found that OLFML2A downregulation clearly suppressed the growth of subcutaneous glioma and intracranial transplantation of glioma by inhibiting Wnt/β-catenin pathway-dependent cell proliferation.Conclusion: Our data indicate the oncogenic effect of OLFML2A in glioma through regulation of Wnt/β-catenin signaling, which may provide a novel therapeutic target for glioma.

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Section: Discussionsupporting

confidence: 74%

OLFML2A Downregulation Inhibits Glioma Proliferation through Suppression of Wnt/β-catenin Signaling

Duan

Dong

et al. 2020

Preprint

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“…OLFML2A and OLFML2B encode for secreted glycoproteins which are closely related to each other [30] . Genomic and GeneChip expression profiling revealed that Amorphophalli Rhizoma inhibited TNBC cells by attenuating OLFML2A [31] . We found that OLFML2A knockdown significantly inhibited the proliferation, migration, and invasion of TNBC cells and promoted the apoptosis of TNBC cells.…”

Section: Discussionmentioning

confidence: 99%

OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein‐1 inhibitor T-5224

Zhao

Zhang

et al. 2021

Translational Oncology

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Highlights Expression of activator protein-1 (AP-1) family is significantly elevated in triple-negative breast cancer (TNBC), compared with that in other breast cancer subtypes. T-5224, an inhibitor of c-Fos/AP-1 resulted in increase of apoptosis and inhibition of proliferation, migration, and invasion of TNBC cells. High OLFML2A level is associated with poor prognosis in TNBC patients that were identified from multiple clinical data sets on line. AP1-overexpressing TNBC dependent on OLFML2A, and targeting both AP-1 and OLFML2A through T‐5224 may be a synergistic therapeutic strategy for this clinically challenging subset of breast cancer.

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“…The regulatory effects analysis shows the possible pathways of upstream regulatory networks and downstream functions that involve the DEGs (26). Consistency score is an indicator used to describe the causal consistency of the upstream regulatory factor in the network, the dataset and dense connection metric between disease and function (27). In total, 33 types of regulatory effects were found (Table SVII).…”

Section: Regulatory Effects Analysismentioning

confidence: 99%

Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes

et al. 2020

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RhoE/Rnd3 is an atypical member of the Rho superfamily of proteins, However, the global biological function profile of this protein remains unsolved. In the present study, a RhoE-knockout H9C2 cardiomyocyte cell line was established using cRISPR/Cas9 technology, following which differentially expressed genes (DEGs) between the knockout and wild-type cell lines were screened using whole genome expression gene chips. A total of 829 DEGs, including 417 upregulated and 412 downregulated, were identified using the threshold of fold changes ≥1.2 and P<0.05. Using the ingenuity pathways analysis system with a threshold of-Log (P-value)>2, 67 canonical pathways were found to be enriched. Many of the detected signaling pathways, including that of oncostatin M signaling, were found to be associated with the inflammatory response. Subsequent disease and function analysis indicated that apart from cardiovascular disease and development function, RhoE may also be involved in other diseases and function, including organismal survival, cancer, organismal injury and abnormalities, cell-to-cell signaling and interaction, and molecular transport. In addition, 885 upstream regulators were enriched, including 59 molecules that were predicated to be strongly activated (Z-score >2) and 60 molecules that were predicated to be significantly inhibited (Z-scores <-2). In particular, 33 regulatory effects and 25 networks were revealed to be associated with the DEGs. Among them, the most significant regulatory effects were 'adhesion of endothelial cells' and 'recruitment of myeloid cells' and the top network was 'neurological disease', 'hereditary disorder, organismal injury and abnormalities'. In conclusion, the present study successfully edited the RhoE gene in H9c2 cells using cRISPR/cas9 technology and subsequently analyzed the enriched DEGs along with their associated canonical signaling pathways, diseases and functions classification, upstream regulatory molecules, regulatory effects and interaction networks. The results of the present study should facilitate the discovery of the global biological and functional properties of RhoE and provide new insights into role of RhoE in human diseases, especially those in the cardiovascular system.

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Genomic and GeneChip expression profiling reveals the inhibitory effects of Amorphophalli Rhizoma in TNBC cells

Cited by 18 publications

References 41 publications

OLFML2A Downregulation Inhibits Glioma Proliferation through Suppression of Wnt/β-catenin Signaling

OLFML2A Downregulation Inhibits Glioma Proliferation through Suppression of Wnt/β-catenin Signaling

OLFML2A is necessary for anti-triple negative breast cancer effect of selective activator protein‐1 inhibitor T-5224

Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes

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