Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis

Xu, Wei; Zeng, Fanning; Li, Songyu; Li, Guihuan; Lai, Xiaorong; Wang, Qiming J.; Deng, Fan

doi:10.1007/s00018-018-2914-9

Cited by 31 publications

(26 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, PC3 Cit20 cells possess levels of glycolysis significantly lower than those of PC3 cells. This change would apparently suggest that PC3 Cit20 cells undergo a metabolic rewiring towards a phenotype less aggressive than the PC3 counterpart [47,48,49]. Indeed, while citrate has been reported to induce cell death in several cell lines via activation of the apoptotic pathway, PC3 Cit20 cells do not show signs of apoptosis, as demonstrated by the lack of Caspase 3 and PARP cleavage.…”

Section: Discussionmentioning

confidence: 99%

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Caiazza

D’Agostino

Passaro

et al. 2019

IJMS

View full text Add to dashboard Cite

Acute administration of a high level of extracellular citrate displays an anti-proliferative effect on both in vitro and in vivo models. However, the long-term effect of citrate treatment has not been investigated yet. Here, we address this question in PC3 cells, a prostate-cancer-derived cell line. Acute administration of high levels of extracellular citrate impaired cell adhesion and inhibited the proliferation of PC3 cells, but surviving cells adapted to grow in the chronic presence of 20 mM citrate. Citrate-resistant PC3 cells are significantly less glycolytic than control cells. Moreover, they overexpress short-form, citrate-insensitive phosphofructokinase 1 (PFK1) together with full-length PFK1. In addition, they show traits of mesenchymal-epithelial transition: an increase in E-cadherin and a decrease in vimentin. In comparison with PC3 cells, citrate-resistant cells display morphological changes that involve both microtubule and microfilament organization. This was accompanied by changes in homeostasis and the organization of intracellular organelles. Thus, the mitochondrial network appears fragmented, the Golgi complex is scattered, and the lysosomal compartment is enlarged. Interestingly, citrate-resistant cells produce less total ROS but accumulate more mitochondrial ROS than control cells. Consistently, in citrate-resistant cells, the autophagic pathway is upregulated, possibly sustaining their survival. In conclusion, chronic administration of citrate might select resistant cells, which could jeopardize the benefits of citrate anticancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Caiazza

D’Agostino

Passaro

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…E2F5 overexpression induced uncontrolled cellular proliferation by up-regulating phosphorylation of SMAD3 and p38 in PCa [26]. The endogenous SMAD2/3 interacted with PKCε to cause SMAD3 to bind to the promoter of glycolysis genes, induced the expression of glycolysis genes HIF-1α, HKII, PFKP and MCT4 and promoted aerobic glycolysis, thereby promoting PCa cell proliferation [27]. In addition, overexpression of SMAD3 could also enhance aerobic glycolysis and PCa cell proliferation in an independent manner that activated protein kinase D or TGF-β [27].…”

Section: Discussionmentioning

confidence: 99%

“…The endogenous SMAD2/3 interacted with PKCε to cause SMAD3 to bind to the promoter of glycolysis genes, induced the expression of glycolysis genes HIF-1α, HKII, PFKP and MCT4 and promoted aerobic glycolysis, thereby promoting PCa cell proliferation [27]. In addition, overexpression of SMAD3 could also enhance aerobic glycolysis and PCa cell proliferation in an independent manner that activated protein kinase D or TGF-β [27]. However, SMAD3 or TGFBR2 null were signi cantly reduced the mass and microvascular density of PCa xenograft tumors [28].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA SNHG16 Functions as Tumor Activator by Sponging hsa-miR-373-3p to Regulate TGFBR2/SMAD Pathway in Prostate Cancer

Weng

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Long noncoding RNAs (lncRNAs) are one of the major causes of tumorigenesis. However, the roles and mechanisms of lncRNA SNHG16 in prostate cancer (PCa) remain unknown. The purpose of this study was to elucidate the mechanisms of lncRNA SNHG16 in the proliferation and metastasis of human PCa cells.Material and Methods: First, the quantitative polymerase chain reaction (qPCR) was used to measure SNHG16 expression in PCa tissues and adjacent normal tissues (n=80). Down-regulate and over-express SNHG16 in human PCa DU-145 cell. Then cell proliferation was detected by CCK8 assay, cell apoptosis was analyzed by flow cytometry, cell migration were determined by wound healing, and cell invasion was examined by transwell. Western blot assays were used to examine the expression of the TGFBR2, c-MYC, E2F4, SMAD2, p-SMAD2, SMAD3, and p-SMAD3. Second, the targeting relationship between SNHG16 and hsa-miR-373-3p was verified by dual-luciferase reporter assay and rescue experiments. Third, the targeting relationship between hsa-miR-373-3p and TGFBR2 was verified by dual-luciferase reporter assay and rescue experiments. Results: The expression of SNHG16 was significant increase in PCa tissues (Z=-8.405, P<0.001), and with significant correlation with patient's age (<60 and ≥60 years old, P=0.007). Silencing SNHG16 inhibited DU-145 cell proliferation, migration, and invasion, while induced cell apoptosis significantly (P<0.01, respectively). Overexpressing SNHG16 promoted cell proliferation, migration and invasion, and reduced cell apoptosis rate (P<0.05, respectively). SNHG16 overexpression observably increased TGFBR2, c-MYC, E2F4, p-SMAD2, and p-SMAD3 expression (P<0.001, respectively), but SNHG16 inhibition was opposite. However, SNHG16 did not regulate SMAD2 and SMAD3 expression. Next, hsa-miR-373-3p was found down-regulated in PCa tissues (Z=-8.344, P<0.001), and the down-regulation of hsa-miR-373-3p were closely linked to Gleason score (Gleason score: <7 and >7, P = 0.024). Hsa-miR-373-3p expression of hsa-miR-373-3p was negatively correlated with SNHG16 (r=-0.544, P<0.001). The result of dual-luciferase reporter assay and qPCR test revealed that hsa-miR-373-3p was a target of SNHG16. Hsa-mir-373-3p inhibitor could rescue sh-SNHG16-inhibited cell proliferation, migration and invasion by promoting TGFBR2, C-MYC, E2F4, P-Smad2, and P-smad3 expression. Finally, we found that TGFBR2 may be the target gene of hsa-mir-373-3p through TargetScan and starbase. Further research found that TGFBR2 was markedly up-regulated in PCa tissues (Z=-5.945, P<0.001), and the expression of TGFBR2 was negatively correlated with hsa-miR-373-3p (r=-0.627, P<0.001). Dual-luciferase reporter assay and qPCR test showed that TGFBR2 was a target of hsa-miR-373-3p. TGFBR2 knockdown could inhibit hsa-mir-373-3p inhibitor-induced cell proliferation, migration and invasion, and reversed the effect of hsa-mir-373-3p inhibitor on cell apoptosis. Based on the data, sh-TGFBR2 partially disabled hsa-mir-373-3p inhibitor effect. Conclusion: LncRNA SNHG16 might act as a ceRNA to regulate the proliferation and migration of DU-145 cells by modulating the hsa-miR-373-3p/TGFBR2/SMAD axis.

show abstract

“…Jin et al (18) found that miR-15a/16 inhibits prostate cancer metastasis and invasion by inhibiting TGF-β signaling pathways. Underexpression or mutation of Smad3 will lead to interruption of TGF-β signaling, making cells beyond the growth inhibition of TGF-β signal pathways and eventually develop into tumor cells (28)(29)(30). Previous studies have shown that Smad3, as a negative growth signal regulator, regulates the expression of TGF-β superfamily during the occurrence and development of varying tumors, accommodates the abnormal growth cycle of cells and protects the body (31,32).…”

Section: Discussionmentioning

confidence: 99%

Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

Guo

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

Effect of targeted regulation of mothers against decapentaplegic homolog 3 (Smad3) by microRNA-15a (miR-15a) on the proliferation, invasion and metastasis of non-small cell lung cancer (NSCLC) cells and its related mechanisms were investigated. Fifty pairs of NSCLC and para-cancerous tissues were collected to identify the expression level of miR-15a in NSCLC, para-cancerous tissue, and cell lines A549, H1299, H1975 and BEAS-2B by real-time fluorescence quantitative PCR (RT-PCR); A549 cells were transfected with miR-15a mimic; the MTT assay was performed to detect the role of miR-15a transfection in proliferation of A549 cells, the wound healing assay was carried out to identify the role of miR-15a in migration of A549 cells; Transwell invasion assay was conducted to analyze the role of miR-15a in invasion of A549 cells; western blotting was carried out to find the effect of miR-15a on Smad3 expression, and Spearman's rank correlation was used to analyze the correlation between miR-15a and Smad3 expression. NSCLC tissues and cells showed significantly lower miR-15a expression, compared with para-cancerous tissues and normal cell lines (P=0.023). miR-15a was significantly more expressed in A549 cells transfected with miR-15a mimic (P=0.043). Overexpression of miR-15a can significantly inhibit A549 cell proliferation (P=0.038), migration (P=0.033) and invasion (P=0.025), and significantly reduced the expression level of Smad3 (P=0.031) in A549 cells. Spearman's rank correlation showed negative correlation of miR-15a expression with Smad3, which may indicate negative regulation (r=-0.34, P<0.0001). Inhibition of proliferation, migration and invasion of NSCLC cells can be achieved with targeted regulation of Smad3 by miR-15a.

show abstract

Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis

Cited by 31 publications

References 64 publications

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Long Noncoding RNA SNHG16 Functions as Tumor Activator by Sponging hsa-miR-373-3p to Regulate TGFBR2/SMAD Pathway in Prostate Cancer

Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

Contact Info

Product

Resources

About

Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis

Cited by 31 publications

References 64 publications

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Effects of Long-Term Citrate Treatment in the PC3 Prostate Cancer Cell Line

Long Non­coding RNA SNHG16 Functions as Tumor Activator by Sponging hsa-miR-373-3p to Regulate TGFBR2/SMAD Pathway in Prostate Cancer

Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

Contact Info

Product

Resources

About

Long Noncoding RNA SNHG16 Functions as Tumor Activator by Sponging hsa-miR-373-3p to Regulate TGFBR2/SMAD Pathway in Prostate Cancer