AMPK/SIRT1 signaling through p38MAPK mediates Interleukin-6 induced neuroendocrine differentiation of LNCaP prostate cancer cells

Natani, Sirisha; Dhople, Vishnu M.; Parveen, Asha; Sruthi, K; Khilar, Priyanka; Bhukya, Supriya; Ummanni, Ramesh

doi:10.1016/j.bbamcr.2021.119085

Cited by 14 publications

(10 citation statements)

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“…An equal amount of protein was loaded onto the sodium dodecyl sulfate‐polyacrylamide gels and resolved by electrophoresis. The Western blot analysis was performed as per the protocol from Natani et al 25 . The list of the antibodies used in this study is provided in the supplementary information.…”

Section: Methodsmentioning

confidence: 99%

“…According to Natani et al RPS15A is one of the differentially expressed proteins regulated upon IL-6 treatments in LNCaP cells. 25 By hypothesizing that the miR-147b is inducing the NED by targetingRPS15A, we have measured the expression levels of RPS15A in all PCa cell line panels (LNCaP, VCaP, PC3, and NCI-H660). Unlike miR-147b, RPS15A expression is decreased at both mRNA and protein levels in neuroendocrine cell line NCI-H660 and PC3 cells with NE features compared to other PCa cells tested indicating that the RPS15A expression is downregulated in NED of PCa (Figure 5B,C).…”

Section: Mir-147b Directly Binds To 3′ Utr Of Rps15a Mrna In Pca Cell...mentioning

confidence: 99%

“…al, the systematic analysis of quantitative proteomics data obtained from IL-6 induced NE differentiated LNCaP cells revealed that RPS15A is downregulated in NE LNCaP cells differentiated with IL-6 in in vitro. 25 RPS15A was identified as a novel target for miR-147b in NSCLC (Nonsmall cell lung carcinoma) cells. 52 Likewise, in our study, we found that downregulation of RPS15A in PC3, NCI-H660 and NE-LNCaP cell lines highlighting a negative correlation between RPS15A and miR-147b expression in both in-vitro differentiated and NE cell lines of PCa.…”

Section: Conflict Of Interest Statementmentioning

confidence: 99%

“…23,24 In our previous studies we reported that IL-6 induces activation of AMPK-SIRT1 and TGF-β signaling pathways and transfers its activation signals to p38MAPK promoting NED of LNCaP cells. 25,26 In addition, ADT affects epithelial-mesenchymal transition (EMT) as evidenced by lower E-cadherin and elevated mesenchymal markers (N-cadherin, vimentin, Zeb1, Twist1, and Snail2). 27 Transfection of LNCaP cells with snail induces NED.…”

Section: Introductionmentioning

confidence: 99%

“…Through STAT3 activation and suppression of RE‐1 silencing transcription factor, IL‐6 induces PCa cells to acquire NE characteristic 23,24 . In our previous studies we reported that IL‐6 induces activation of AMPK‐SIRT1 and TGF‐β signaling pathways and transfers its activation signals to p38MAPK promoting NED of LNCaP cells 25,26 . In addition, ADT affects epithelial‐mesenchymal transition (EMT) as evidenced by lower E‐cadherin and elevated mesenchymal markers (N‐cadherin, vimentin, Zeb1, Twist1, and Snail2) 27 .…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

et al. 2023

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Background Prostate cancer (PCa) is the leading cause of cancer related deaths in men, often androgen deprivation therapy (ADT) leads to the progression of androgen independent PCa (AIPC) which further leads to Neuroendocrine PCa (NEPC). Identifying the molecular mechanisms which navigate the neuroendocrine differentiation (NED) of PCa cells is clinically relevant. It has been suggested that the micro RNAs (miRNAs) play an important role in the regulation of intrinsic mechanisms relevant to tumor progression, resistance as a result leads to poor prognosis. miR‐147b has been transpiring as one of the deregulated miRNAs associated with the occurrence of multiple cancers. The present study has studied the role of miRNA‐147b in inducing NEPC. Methods To investigate the functional role of miR‐147b in NEPC, we have expressed miRNA mimics or inhibitors in PCa cells and monitored the progression of NEPC along with PCa cell proliferation and survival. The molecular mechanism miRNA‐147b follows was studied using western blot and reverse transcription polymerase chain analysis. miRNA target prediction using bioinformatics tools followed by target validation using luciferase reporter assays was performed. Results In the present study, we found that miR‐147b is highly expressed in AIPC cell lines in particular neuroendocrine cells NCI‐H660 and NE‐LNCaP derived from LNCaP. Mechanistic studies revealed that overexpression of miR‐147b or miRNA mimics induced NED in LNCaP cells in in‐vitro while its inhibitor reversed the NE features (increased NE markers and reduced prostate specific antigen) of PC3, NCI‐H660 and NE‐LNCaP cells. In addition, miR‐147b reduced the proliferation rate of LNCaP cells via elevated p27kip1 and lowered cyclin D1 for promoting differentiation. In reporter assays, we have identified ribosomal protein S15A (RPS15A) is a direct target of miRNA‐147b and RPS15A expression was negatively regulated by miR‐147b in PCa cells. Furthermore, we also report that RPS15A is downregulated in NEPC cells and its expression is inversely correlated with NE markers. Conclusion Targeting the miR‐147b ‐ RPS15A axis may overcome the progression of NEPC and serve as a novel therapeutic target to attenuate NED progression of PCa.

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Section: Methodsmentioning

confidence: 99%

Section: Mir-147b Directly Binds To 3′ Utr Of Rps15a Mrna In Pca Cell...mentioning

confidence: 99%

Section: Conflict Of Interest Statementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

et al. 2023

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Induction of more aggressive tumoral phenotypes in LNCaP and PC3 cells by serum exosomes from prostate cancer patients

Huertas‐Lárez

Muñoz‐Moreno

Recio‐Aldavero

et al. 2023

Intl Journal of Cancer

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Prostate cancer (PCa) is the second most frequent and sixth most fatal cancer in men worldwide. Despite its high prevalence, our understanding of its etiology and the molecular mechanisms involved in the progression of the disease is substantially limited. In recent years, the potential participation of exosomes in this process has been suggested. Therefore, we aim to study the effect of exosomes isolated from the serum of patients with PCa on various cellular processes associated with increased tumor aggressiveness in two PCa cell lines: LNCaP‐FGC and PC3. The exosomes were isolated by filtration wand ultracentrifugation. Their presence was confirmed by immunodetection of specific markers and their size distribution was analyzed by Dynamic Light Scattering (DLS). The results obtained demonstrated that serum exosomes from PCa patients increased migration of PC3 cells and neuroendocrine differentiation of LNCaP‐FGC cells regardless of the grade of the tumor. PCa serum exosomes also enhanced the secretion of enzymes related to invasiveness and resistance to chemotherapeutics, such as extracellular matrix metalloproteases 2 and 9, and gamma‐glutamyltransferase in both cell lines. Altogether, these findings support the pivotal participation of exosomes released by tumoral cells in the progression of PCa. Future studies on the molecular mechanisms involved in the observed changes could provide crucial information on this disease and help in the discovery of new therapeutic targets.

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Chlamydia psittaci plasmid-encoded CPSIT_P7 induces macrophage polarization to enhance the antibacterial response through TLR4-mediated MAPK and NF-κB pathways

Wang

Huang

et al. 2022

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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AMPK/SIRT1 signaling through p38MAPK mediates Interleukin-6 induced neuroendocrine differentiation of LNCaP prostate cancer cells

Cited by 14 publications

References 64 publications

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

MicroRNA‐147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A

Induction of more aggressive tumoral phenotypes in LNCaP and PC3 cells by serum exosomes from prostate cancer patients

Chlamydia psittaci plasmid-encoded CPSIT_P7 induces macrophage polarization to enhance the antibacterial response through TLR4-mediated MAPK and NF-κB pathways

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