High SPRR1A expression is associated with poor survival in patients with colon cancer

Deng, Yu; Zheng, Xin; Zhang, Yiyi; Xu, Meifang; Ye, Chengwei; Lin, Min; Pan, Jie; Xu, Zongbin; Lu, Xingrong; Chi, Pan

doi:10.3892/ol.2020.11453

Cited by 6 publications

(8 citation statements)

References 17 publications

(30 reference statements)

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“…In the current study, we also demonstrate that LV SPRR1A was upregulated in patients with HFrEF ( Figure 5C ), which is consistent with reports in mice with ISO-induced myocardial injury ( 30 ) and renal I/R injury ( 31 ). Interestingly, SPRR1A expression was also reported to be inversely linked with survival of cancer patients ( 37 – 39 ). Here, we also show that Sprr1a was downregulated in hearts and CMs by Carv ( Supplemental Figure 10 ), concurrent with upregulation of miR-150 ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline–rich protein 1A

Aonuma¹,

Moukette²,

Kawaguchi³

et al. 2021

JCI Insight

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MicroRNA-150 (miR-150) is downregulated in patients with multiple cardiovascular diseases and in diverse mouse models of heart failure (HF). miR-150 is significantly associated with HF severity and outcome in humans. We previously reported that miR-150 is activated by β-blocker carvedilol (Carv) and plays a protective role in the heart using a systemic miR-150 KO mouse model. However, mechanisms that regulate cell-specific miR-150 expression and function in HF are unknown. Here, we demonstrate that potentially novel conditional cardiomyocyte–specific (CM-specific) miR-150 KO (miR-150 cKO) in mice worsens maladaptive cardiac remodeling after myocardial infarction (MI). Genome-wide transcriptomic analysis in miR-150 cKO mouse hearts identifies small proline–rich protein 1a ( Sprr1a ) as a potentially novel target of miR-150. Our studies further reveal that Sprr1a expression is upregulated in CMs isolated from ischemic myocardium and subjected to simulated ischemia/reperfusion, while its expression is downregulated in hearts and CMs by Carv. We also show that left ventricular SPRR1A is upregulated in patients with HF and that Sprr1a knockdown in mice prevents maladaptive post-MI remodeling. Lastly, protective roles of CM miR-150 are, in part, attributed to the direct and functional repression of proapoptotic Sprr1a . Our findings suggest a crucial role for the miR-150/SPRR1A axis in regulating CM function post-MI.

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Section: Discussionmentioning

confidence: 99%

Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline–rich protein 1A

Aonuma¹,

Moukette²,

Kawaguchi³

et al. 2021

JCI Insight

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“…Squamous differentiation, unlike the adenocarcinoma component, essentially expresses SPRR1A , as described above. After verifying that the expression of keratin 5 (KRT5) did not correlate with that of SPRR1A ( S3B Fig ), we used the same method as in S1C and S1D Fig to exclude the eight patients with high transcript levels of KRT5 , a squamous epithelial marker [ 19 ], above the average plus two s.d. ( S3C Fig ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that SPRR3 promoted the proliferation of breast cancer and colorectal cancer cells via the AKT and mitogen-activated protein kinase (MAPK) pathways [ 16 , 17 ] and that SPRR2B facilitated the growth of gastric cancer via the MDM2-p53/p21 signaling pathway [ 18 ], suggesting that SPRR family genes may be involved in cancer growth signaling. Furthermore, recent studies have reported the prognostic value of a high expression of SPRR1A in colon cancer, breast cancer and diffuse large B-cell lymphoma [ 19 – 21 ]. We have also found that SPRR1A may be associated with the characteristics of cancer stem cells derived from osteosarcoma [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Increased expression of SPRR1A is associated with a poor prognosis in pancreatic ductal adenocarcinoma

et al. 2022

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Objectives Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Methods We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro. Results Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression. Conclusion Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC.

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“…(C and D) Tumor volumes were measured every five days and calculated as described in the Method section, which revealed that SPRR2B-shRNA significantly attenuated tumor growth while overexpressing SPRR2B exerted opposite effects. malignancy progression, such as SPRR1A, [25][26][27][28] SPRR1B, [29][30][31] SPRR2A, [32][33][34][35] and SPRR3. [36][37][38][39] However, SPRRs can serve as either tumor suppressors 39 or oncoproteins 38 in different malignancies.…”

Section: Discussionmentioning

confidence: 99%

Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway

Yao¹,

Yan²,

Cheng³

et al. 2021

OTT

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Background The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression. Methods Immunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo. Results Both mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects. Conclusion Our data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.

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High SPRR1A expression is associated with poor survival in patients with colon cancer

Cited by 6 publications

References 17 publications

Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline–rich protein 1A

Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline–rich protein 1A

Increased expression of SPRR1A is associated with a poor prognosis in pancreatic ductal adenocarcinoma

Small Proline-Rich Protein 2B Facilitates Gastric Adenocarcinoma Proliferation via MDM2-p53/p21 Signaling Pathway

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