GNA13 promotes the proliferation and migration of lung squamous cell carcinoma cells through regulating the PI3K/AKT signaling pathway

Na, Jianrong; Zhou, Wei; Yin, Mei; Hu, Yingchun; Xuan, Ming

doi:10.1016/j.tice.2022.101795

“…Similar conclusions were reached in the present experiment, where we found that VRK1 expression levels were signifcantly higher in lung cancer tumor tissues than in normal tissues, as well as in the relevant assays of clinical data. Tis shows that the expression of VRK1 is closely related to the development of LUSC.NCI-H520 and SK-MES-1 are two common LUSC cell lines, through which Na et al found that the knockdown of GNA13 could inhibit LUSC [17]. In the present study, it was also found that VRK1 expression was highest in both NCI-H520 and SK-MES-1 cell lines, and the cell viability of NCI-H520 and SK-MES-1 in the shVRK1 group was signifcantly lower than that in the shNC group, and SK-MES-1 in the shVRK1 group had signifcantly lower cell viability than in the shNC group.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage

Du

¹

,

Zhang

²

,

Zhang

³

2023

Canadian Respiratory Journal

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Background. Lung squamous cell carcinoma (LUSC) is a common malignancy. And the antitumor effect of bovine pox virus-associated kinase 1 (VRK1) is becoming a hot research topic. Methods. VRK1 expression and prognosis in LUSC were analyzed using the GEPIA database. The expression of VRK1 mRNA was detected in 25 LUSC clinical tissue samples by RT-PCR. VRK1 shRNA was transfected into LUSC NCI-H520 and SK-MES-1 cell lines to interfere with VRK1 expression, and the efficiency of VRK1 shRNA interference was detected by the western blot. The effects of VRK1 downregulation on LUSC cell viability, migration, cell cycle, and apoptosis were analyzed by the CCK8 assay, scratch assay, transwell assay, and flow cytometry. The effect of VRK1 downregulation on DNA damage response (DDR) was examined by immunofluorescence staining and western blot assays and further validated by in vivo experiments. Results. VRK1 was highly expressed in both LUSC tissues and cells. Survival analysis showed that the overall survival of LUSC patients with high VRK1 expression was significantly lower than that of LUSC patients with low VRK1 expression ( P = 0.0026 ). The expression level of the VRK1 gene was significantly higher in cancer tissues of LUSC patients than in paracancerous tissues. After transfection of VRK1 shRNA in both LUSC cells, cell activity decreased ( P < 0.001 ), migration ability started to be inhibited ( P < 0.001 ), the ratio of G0/G1 phase cells increased ( P < 0.001 ), and apoptosis rate increased ( P < 0.001 ). Immunofluorescence and western blot results showed that shVRK1 increased the level of γ-H2A.X ( P < 0.001 ) and promoted apoptosis of tumor cells ( P < 0.001 ). In addition, the results of animal experiments showed that shVRK1 had antitumor effects ( P < 0.001 ) and a combined effect with DOX ( P < 0.001 ). Conclusion. The downregulation of VRK1 significantly affected the proliferation, apoptosis, migration, and cell cycle progression of LUSC cells via DDR, suggesting that VRK1 is a suitable target for potential LUSC therapy.

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Identification of Potential Biomarkers Using Integrative Approach: A Case Study of ESCC

Saikia

¹

,

Bhattacharyya

²

,

Kalita

³

2022

SN COMPUT. SCI.

1

0

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This paper presents a consensus-based approach that incorporates three microarray and three RNA-Seq methods for unbiased and integrative identification of differentially expressed genes (DEGs) as potential biomarkers for critical disease(s). The proposed method performs satisfactorily on two microarray datasets (GSE20347 and GSE23400) and one RNA-Seq dataset (GSE130078) for esophageal squamous cell carcinoma (ESCC). Based on the input dataset, our framework employs specific DE methods to detect DEGs independently. A consensus based function that first considers DEGs common to all three methods for further downstream analysis has been introduced. The consensus function employs other parameters to overcome information loss. Differential co-expression (DCE) and preservation analysis of DEGs facilitates the study of behavioral changes in interactions among DEGs under normal and diseased circumstances. Considering hub genes in biologically relevant modules and most GO and pathway enriched DEGs as candidates for potential biomarkers of ESCC, we perform further validation through biological analysis as well as literature evidence. We have identified 25 DEGs that have strong biological relevance to their respective datasets and have previous literature establishing them as potential biomarkers for ESCC. We have further identified 8 additional DEGs as probable potential biomarkers for ESCC, but recommend further in-depth analysis.

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GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene

Subramanyan,

Rasheed,

Wang

et al. 2024

Breast Cancer Res

0

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GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers. In most cases, Gα12 and Gα13, as closely related α-subunits in the subfamily, have similar cellular roles. However, in recent years their differences in signaling and function have started to emerge. We previously identified that Gα13 drives invasion of Triple Negative Breast Cancer (TNBC) cells in vitro. As a highly heterogenous disease with various well-defined molecular subtypes (ER+ /Her2−, ER+ /Her2+, Her2+, TNBC) and subtype associated outcomes, the function(s) of Gα13 beyond TNBC should be explored. Here, we report the finding that low expression of GNA13 is predictive of poorer survival in breast cancer, which challenges the conventional idea of Gα12/13 being universal oncogenes in solid tumors. Consistently, we found that Gα13 suppresses the proliferation in multiple ER+ breast cancer cell lines (MCF-7, ZR-75-1 and T47D). Loss of GNA13 expression drives cell proliferation, soft-agar colony formation and in vivo tumor formation in an orthotopic xenograft model. To evaluate the mechanism of Gα13 action, we performed RNA-sequencing analysis on these cell lines and found that loss of GNA13 results in the upregulation of MYC signaling pathways in ER+ breast cancer cells. Simultaneous silencing of MYC reversed the proliferative effect from the loss of GNA13, validating the role of MYC in Gα13 regulation of proliferation. Further, we found Gα13 regulates the expression of MYC, at both the transcript and protein level in an ERα dependent manner. Taken together, our study provides the first evidence for a tumor suppressive role for Gα13 in breast cancer cells and demonstrates for the first time the direct involvement of Gα13 in ER-dependent regulation of MYC signaling. With a few exceptions, elevated Gα13 levels are generally considered to be oncogenic, similar to Gα12. This study demonstrates an unexpected tumor suppressive role for Gα13 in ER+ breast cancer via regulation of MYC, suggesting that Gα13 can have subtype-dependent tumor suppressive roles in breast cancer.

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GNA13 promotes the proliferation and migration of lung squamous cell carcinoma cells through regulating the PI3K/AKT signaling pathway

Cited by 4 publications

References 13 publications

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage

Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage

Identification of Potential Biomarkers Using Integrative Approach: A Case Study of ESCC

GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene

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