The miR-124-Prolyl Hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression

Chakravarthi, Balabhadrapatruni V. S. K.; Pathi, Satya S.; Goswami, Moloy T.; Cieślik, Marcin; Zheng, Heng; Nallasivam, Sivakumar; Arekapudi, Subramanyeswara R.; Jing, Xiaojun; Siddiqui, Javed; Athanikar, Jyoti N.; Carskadon, Shannon; Lonigro, Robert J.; Kunju, Lakshmi P.; Chinnaiyan, Arul M.; Palanisamy, Nallasivam; Varambally, Sooryanarayana

doi:10.18632/oncotarget.2208

Cited by 86 publications

(100 citation statements)

References 51 publications

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“…The effect of hypoxia caused by DM and gingivitis in the present study revealed an expression of P4HA1 was in agreement with Chakravarthi et al (2014) who reported that hypoxia increase the expression of P4HA1& P4HA2 in breast cancer (16) The effect HA gel 0.8% on DM associated with gingivitis and on the expression of P4HA1 in the present study was in agreement with Zhu et al (2015) who reported significantly accelerated healing of rat palatal wound which was related to the decreased effect of hypoxia and reduction in P4Hs action, by topical application of dimethyloxalylglycine with hyaluronic acid ointment (17) The present study showed a favurable expression of Prolyl 4 hydroxylase in treatment of plaque induced gingivitis modified with DM, using hyaluronan than other included groups.…”

Section: Discussionsupporting

confidence: 92%

Effect of Topically- Applied Hyaluronan on the Expression of Prolyl 4- Hydroxylase in Gingivitis of Diabetic Rats

Nahla

Sheikh²,

Gawish³

2017

ADJ-for Girls

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Objective:To evaluate the effect of topically applied hyaluronic acid gel (hyaluranon) on gingivitis in diabetic rats. The evaluation based on clinical, histological, and immunohistochemical analysis. Materials and Methods:The present study included seventy rats were included in this study, sixty rats were divided into two main groups according to treatment modality, group I involved thirty rats treated with topical HA, while group II involved thirty rats left untreated. Furthermore groups I and II subdivided into subgroups Ia, IIa were sacrificed on the seventh day, and subgroups Ib, IIb were sacrificed was sacrificed on the day fourteen, negative control compromised five healthy rats, and positive control group compromised five diabetic rats. Harvested gingival specimens were fixed in formalin, then embedded in paraffin wax, and serially sectioned at 4µm for immunohistochemical assessment using Prolyl 4 Hydroxylase A1(P4HA1). Results: Immunohistochemical evaluation using P4HA1 revealed a significant difference between all groups.

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Section: Discussionsupporting

confidence: 92%

Effect of Topically- Applied Hyaluronan on the Expression of Prolyl 4- Hydroxylase in Gingivitis of Diabetic Rats

Nahla

Sheikh²,

Gawish³

2017

ADJ-for Girls

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“…In this study, we demonstrated that E2 could upregulate or downregulate certain miRNAs, and miR-124 was the most prominently downregulated miRNA which is regulated by E2 treatment in ER-positive BC cells. miR-124 has been reported to act as a tumor suppresser in many cancers including BC [30–32]. In this study, we discovered that estrogen-regulated miR-124 plays an important role in BC cell proliferation, migration, invasion, tumor growth and angiogenesis, and also identified that miR-124 suppression caused by E2 in ER-positive BC cells is through ERα instead of ERβ.…”

Section: Discussionmentioning

confidence: 67%

Estrogen regulates miRNA expression: implication of estrogen receptor and miR-124/AKT2 in tumor growth and angiogenesis

Jiang

Shi

et al. 2016

Oncotarget

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It is currently known that estrogen plays an important role in breast cancer (BC) development, but the underlying molecular mechanism remains to be elucidated. Accumulating evidence has revealed important roles of microRNAs in various kinds of human cancers, including BC. In this study, we found that among the microRNAs regulated by estrogen, miR-124 was the most prominent downregulated miRNA. miR-124 was downregulated by estradiol (E2) treatment in estrogen receptor (ER) positive BC cells, miR-124 overexpression suppressed cell proliferation, migration and invasion in BC cells; while the suppression of miR-124 using Anti-miR-124 inhibitor had opposite cellular functions. Under the E2 treatment, miR-124 had stronger effect to inhibit cellular functions in MCF7 cells than that in MDA-MB-231 cells. In addition, we identified that ERα, but not ERβ, was required for E2-induced miR-124 downregulation. Furthermore, AKT2, a known oncogene, was a novel direct target of miR-124. AKT2 expression levels were inversely correlated with miR-124 expression levels in human breast cancer specimens. AKT2 was overexpressed in BC specimens, and its expression levels were much higher in ERα positive cancer tissues than those ERα negative cancer tissues. Consistent with miR-124 suppression, E2 treatment increased AKT2 expression levels in MCF7 cells via ERα. Finally, overexpression of miR-124 in MCF7 cells significantly suppressed tumor growth and angiogenesis by targeting AKT2. Our results provide a mechanistic insight into a functional role of new ERα/miR-124/AKT2 signaling pathway in BC development. miR-124 and AKT2 may be used as biomarkers for ERα positive BC and therapeutic effect in the future.

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“…11–13, 36, 37 To investigate the potential targets of microRNA-101, we utilized freely available web-based micoRNA target prediction resources; TargetScan, 38 miRanda 39 and Diana-microT. 40 We identified miR-101 that could potentially target SUB1.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

et al. 2016

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MicroRNA-101, a tumor suppressor microRNA is often down-regulated in cancer and is known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2, COX2, POMP, CERS6, STMN1, MCL-1 and ROCK2, among others. In the present study, we show that mir-101 targets transcriptional coactivator SUB1 homolog (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) and regulates its expression. SUB1 is known to play diverse role in vital cell processes such as DNA replication, repair and heterochromatinization. SUB1 is known to modulate transcription and acts as a mediator between the upstream activators and general transcription machinery. Expression profiling in several cancers revealed SUB1 overexpression, suggesting a potential role in tumorigenesis. However, detailed regulation and function of SUB1 has not been elucidated. In this study, we show elevated expression of SUB1 in aggressive prostate cancer. Knockdown of SUB1 in prostate cancer cells resulted in reduced cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Gene expression analyses coupled with chromatin immunoprecipitation revealed that SUB1 binds to the promoter regions of several oncogenes such as polo-like kinase PLK1, C-MYC, serine threonine kinase BUB1B and regulates their expression. Additionally, we observed SUB1 down-regulated CDKN1B expression. PLK1 knockdown or use of PLK1 inhibitor can mitigate oncogenic function of SUB1 in benign prostate cancer cells. Thus, our study suggests that miR-101 loss results in increased SUB1 expression and subsequent activation of known oncogenes driving prostate cancer progression and metastasis. This study therefore demonstrates functional role of SUB1 in the prostate cancer and identifies its regulation, and potential downstream therapeutic targets of SUB1 in prostate cancer.

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The miR-124-Prolyl Hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression

Cited by 86 publications

References 51 publications

Effect of Topically- Applied Hyaluronan on the Expression of Prolyl 4- Hydroxylase in Gingivitis of Diabetic Rats

Effect of Topically- Applied Hyaluronan on the Expression of Prolyl 4- Hydroxylase in Gingivitis of Diabetic Rats

Estrogen regulates miRNA expression: implication of estrogen receptor and miR-124/AKT2 in tumor growth and angiogenesis

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

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