<i>SERPINB5</i> Genetic Variants rs2289519 and rs2289521 are Significantly Associated with Gallbladder Cancer Risk

Mahananda, Biswaheree; Vinay, J.; Palo, Ananya; Singh, Ayaskanta; Sahu, Swagatika; Singh, Shivaram Prasad; Dixit, Manjusha

doi:10.1089/dna.2021.0056

Cited by 10 publications

(8 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serpin family B member 5 (SERPINB5), located on chromosome 18q21.33 as a tumor suppressor gene, plays a critical in cancer cell invasion and metastasis. SERPINB5 variants are significantly associated with gallbladder cancer risk (43). Upregulated Maspin inhibited the expression of IKKα to promote cell apoptosis and delayed the development of the precancerous lesions in precancerous rats (44).…”

Section: Discussionmentioning

confidence: 99%

The identification of hub biomarkers and pathways in lung cancer and prognostic evaluation

Yin¹,

Liu²,

He³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Lung cancer is the most frequently diagnosed malignant tumor and the highest mortality worldwide, and can be divided into two differential histologic subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, there are significant differences in diagnosis and prognosis between NSCLC and SCLC. We aimed to identify hub differentially expressed genes (DEGs) and pathways for diagnostic and prognostic prediction in NSCLC and SCLC.Methods: Three expression profiles (GSE43346, GSE40275 and GSE18842) were obtained through GEO2R tools from Gene Expression Omnibus (GEO) database. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to investigate functional enrichment of the DEGs. The protein-protein interaction network was constructed by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Kaplan-Meier analysis was performed using Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). Results:We have identified 84 overlap DEGs that may play an important role in SCLC & NSCLC.However, we also found some genes were only significantly differential expressed in SCLC or NSCLC.There were 87 DEGs unique to SCLC tissues and 28 DEGs unique to NSCLC ones. Functional analysis results indicated that these DEGs had different biological functions and were significantly enriched in different pathways. Hub DEGs were identified via protein-protein interaction network and cross-validated using Kaplan-Meier plotter and GEPIA. The 14 hub DEGs were highly correlated with the overall survival of NSCLC. Kyoto Encyclopedia of Genes and Genome (KEGG) re-analysis of 14 hub DEGs showed that RRM2, CHEK1 and SERPINB5 enriched in the p53 signaling pathway, RRM2 and TYMS enriched in pyrimidine metabolism pathway maybe play a key role in SCLC&NSCLC and were significantly related to overall survival in patients with NSCLC.Conclusions: RRM2, CHEK1, TYMS and SERPINB5, which are mainly enriched in the p53 signaling pathway and pyrimidine metabolism pathway, were significantly associated with the overall survival of NSCLC patients. These genes could serve as potential prognostic markers in NSCLC and therapeutic target in lung cancer for personalized oncology.

show abstract

Section: Discussionmentioning

confidence: 99%

The identification of hub biomarkers and pathways in lung cancer and prognostic evaluation

Yin¹,

Liu²,

He³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…29 It has been stated that SERPINB5 genetic variation is closely related to the occurrence of GBC. 30,31 Dong's research group reported that SERPINB5 reduces the accumulation of matrix metalloproteinases MMP2 and MMP9 to decelerate the migration and invasion processes of GBC cells. 32 However, the Snail.…”

Section: Studies Have Shown That Foxa2 Can Participate In Cancer Init...mentioning

confidence: 99%

FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial‐mesenchymal transition by targeting SERPINB5

Hong,

Chen,

Huang

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

BackgroundGallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial‐mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC.MethodsFOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT‐PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual‐luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism.ResultsFOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression.ConclusionFOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC.

show abstract

“…22 Additionally, the homozygous maspin-S176 has been linked with gallbladder cancer. 23 However, how a minor variation in the unstructured region can drastically alter the function of an antitumor protein to protumor protein is still a mystery. Structural biology has advanced our understanding of the three-dimensional structures of different proteins; however, the lack of a dynamic picture of these proteins hinders their functional aspects.…”

Section: Introductionmentioning

confidence: 99%

“…Maspin-P176, in conjunction with maspin-L187, decreases the risk of esophageal squamous cell carcinoma, whereas maspin-S176 (with maspin-V187) exerts the opposite effect . Additionally, the homozygous maspin-S176 has been linked with gallbladder cancer . However, how a minor variation in the unstructured region can drastically alter the function of an antitumor protein to protumor protein is still a mystery.…”

Section: Introductionmentioning

confidence: 99%

P176S Mutation Rewires Electrostatic Interactions That Alter Maspin Functionality

et al. 2023

View full text Add to dashboard Cite

Maspin is known to regress tumors by inhibiting angiogenesis; however, its roles have been reported to be context- and sequence-dependent. Various proteins and cofactors bind to maspin, possibly explaining its conflicting roles. Moreover, polymorphic forms of maspin have also been linked to tumor regression and survival; for instance, maspin with Ser at 176 (maspin-S176) promotes tumors, while maspin with Pro at 176 (maspin-P176) has opposing roles in cancer pathogenesis. With the help of long molecular dynamics simulations, a possible link between polymorphic forms and tumor progression has been established. First, maspin is dynamically stable with either amino acid at the 176 position. Second, differential contacts have been observed among various regions; third, these contacts have significantly altered the electrostatic energetics of various residues; finally, these altered electrostatics of maspin-S176 and maspin-P176 rewire the polar contacts that abolished the allosteric control of the protein. By combining these factors, the altered electrostatics substantially affect the localization and preference of maspin-binding partners, thus culminating in a different maspin-protein(cofactor)-interaction landscape that may have been manifested in previous conflicting reports. Here, the underlying reason has been highlighted and discussed, which may be helpful for better therapeutic manipulation.

show abstract

SERPINB5 Genetic Variants rs2289519 and rs2289521 are Significantly Associated with Gallbladder Cancer Risk

Cited by 10 publications

References 33 publications

The identification of hub biomarkers and pathways in lung cancer and prognostic evaluation

The identification of hub biomarkers and pathways in lung cancer and prognostic evaluation

FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial‐mesenchymal transition by targeting SERPINB5

P176S Mutation Rewires Electrostatic Interactions That Alter Maspin Functionality

Contact Info

Product

Resources

About