MicroRNA-375 inhibits the proliferation, migration and invasion of kidney cancer cells by triggering apoptosis and modulation of PDK1 expression

Wang, Jinling; Sun, Xiuju

doi:10.1016/j.etap.2018.08.002

Cited by 17 publications

(21 citation statements)

References 27 publications

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“…Many genes involved in oxygen sensing, chromatin stabilization and cell metabolism are abnormally expressed in renal cancer cells 26. Despite the development of therapeutic methods, frequent recurrences and treatments have many side effects 27. Therefore, there is an urgent need to explore novel specific therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

<p>Overexpressed miR-122-5p Promotes Cell Viability, Proliferation, Migration And Glycolysis Of Renal Cancer By Negatively Regulating PKM2</p>

Wang

Zheng

et al. 2019

CMAR

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ObjectiveRenal cancer is one of the most deadly urological malignancies. Currently, there is still a lack of effective treatment. Our purpose was to explore the mechanisms of miR-122-5p in renal cancer.MethodsThe expression levels of miR-122-5p and pyruvate kinase M2 (PKM2) in renal cancer cells were detected by RT-qPCR and Western blot analyses, respectively. Then, we measured the cell viability after knockdown of miR-122-5p and PKM2 using CCK-8 assay. Moreover, flow cytometry was used to investigate cell cycle and apoptosis of renal cancer cells. The cell migration of renal cancer cells transfected by miR-122-5p inhibitor and siPKM2 was then detected by wound healing assay. Furthermore, glucose consumption and lactate production were measured. Autophagy-related protein LCII/I was detected by Western blot.ResultsMiR-122-5p was upregulated in renal cancer cells compared to HK2 cells, especially in 786-O cells. We found that silencing miR-122-5p promoted PKM2 expression in 786-O cells. After transfection of siPKM2 or miR-122-5p inhibitor, the cell viability of 786-O cells was significantly reduced. Furthermore, the G1 phase of 786-O cells was significantly blocked, and the S phase was significantly increased. In addition, knockdown of miR-122-5p or PKM2 promoted renal cancer cell apoptosis and inhibited cell migration. Glucose consumption of 786-O cells was significantly increased after transfection by siPKM2. Silencing miR-122-5p significantly promoted the expression levels of LCII/I.ConclusionOur findings revealed that overexpressed miR-122-5p promotes renal cancer cell viability, proliferation, migration, glycolysis and autophagy by negatively regulating PKM2, which provide a new insight for the development of renal cancer therapy.

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Section: Discussionmentioning

confidence: 99%

<p>Overexpressed miR-122-5p Promotes Cell Viability, Proliferation, Migration And Glycolysis Of Renal Cancer By Negatively Regulating PKM2</p>

Wang

Zheng

et al. 2019

CMAR

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“…PDK1-pS241 is produced by the gene PDK1 according to the TCPA database and is overexpressed in many types of cancer (Wang et al, 2019). Previous reports have suggested that PDK1 plays an important role in cancer (Wang and Sun, 2018), and it is often modified by microRNAs or used as a drug target (Zhou et al, 2017;Wang and Sun, 2018;Wang et al, 2019). The utility of PDK1-pS241 was similar to that of MAPK-pT202Y204, showing beneficial effects for ccRCC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Protein-Based Signature to Improve Prognosis Prediction in Renal Clear Cell Carcinoma

Chu

Zhu

et al. 2021

Front. Mol. Biosci.

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BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney cancer, and its incidence and mortality are not optimistic. It is well known that tumor-related protein markers play an important role in cancer detection, prognosis prediction, or treatment selection, such as carcinoembryonic antigen (CEA), programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4), so a comprehensive analysis was performed in this study to explore the prognostic value of protein expression in patients with ccRCC.Materials and MethodsProtein expression data were obtained from The Cancer Proteome Atlas (TCPA), and clinical information were downloaded from The Cancer Genome Atlas (TCGA). We selected 445 patients with complete information and then separated them into a training set and testing set. We performed univariate, least absolute shrinkage and selection operator (LASSO) Cox analyses to find prognosis-related proteins (PRPs) and constructed a protein signature. Then, we used stratified analysis to fully verify the prognostic significance of the prognostic-related protein signature score (PRPscore). Besides, we also explored the differences in immunotherapy response and immune cell infiltration level in high and low score groups. The consensus clustering analysis was also performed to identify potential cancer subgroups.ResultsFrom the training set, a total of 233 PRPs were selected, and a seven-protein signature was constructed, including ACC1, AR, MAPK, PDK1, PEA15, SYK, and BRAF. Based on the PRPscore, patients could be divided into two groups with significantly different overall survival rates. Univariate and multivariate Cox regression analyses proved that this signature was an independent prognostic factor for patients (P < 0.001). Moreover, the signature showed a high ability to distinguish prognostic outcomes among subgroups, and the low score group had a better prognosis (P < 0.001) and better immunotherapy response (P = 0.003) than the high score group.ConclusionWe constructed a novel protein signature with robust predictive power and high clinical value. This will help to guide the disease management and individualized treatment of ccRCC patients.

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“…Previously, PDPK1 has received considerable attention as a critical factor regulating cell proliferation, apoptosis and metastasis of various cancer cells (38-41). Furthermore, PDPK1 has been demonstrated as the functional downstream target of numerous miRNAs (42-45). As evidenced by the luciferase assay results in the present study, miR-16-2-3p significantly repressed PDPK1 expression through directly regulating the 3′-UTR of PDPK1.…”

Section: Discussionmentioning

confidence: 99%

miR‑16‑2‑3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in�maxillary primordium mesenchymal cells

Han

Wang

et al. 2019

Int J Mol Med

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MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by targeting the 3' untranslated region (UTR) of target genes, and serve diverse roles in cell proliferation, differentiation and apoptosis. However, the association between miR-16-2-3p and 3-phosphoinositide-dependent protein kinase-1 (PdPK1) in nonsyndromic cleft lip (NScL) remains unclear. In the present study, a luciferase activity assay indicated that miR-16-2-3p negatively regulated PdPK1 in maxillary primordium mesenchymal cells (MPMcs). In addition, it was confirmed that the expression levels of miR-16-2-3p was markedly increased in cleft lip tissues compared with those in adjacent normal lip tissues. A negative correlation between miR-16-2-3p and PdPK1 in cleft lip tissues was observed. Furthermore, miR-16-2-3p inhibited cell proliferation and migration, and induced apoptosis of MPMcs via repressing PdPK1. Finally, miR-16-2-3p exerted its suppressive role in MPMcs by inhibiting the PdPK1/protein kinase B signaling pathway. These results indicate that miR-16-2-3p may inhibit cell proliferation and migration, and promote apoptosis in MPMcs through repression of PdPK1 and may be a potential target for future clinical prevention and treatment of NScL.

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MicroRNA-375 inhibits the proliferation, migration and invasion of kidney cancer cells by triggering apoptosis and modulation of PDK1 expression

Cited by 17 publications

References 27 publications

<p>Overexpressed miR-122-5p Promotes Cell Viability, Proliferation, Migration And Glycolysis Of Renal Cancer By Negatively Regulating PKM2</p>

<p>Overexpressed miR-122-5p Promotes Cell Viability, Proliferation, Migration And Glycolysis Of Renal Cancer By Negatively Regulating PKM2</p>

Identification of a Novel Protein-Based Signature to Improve Prognosis Prediction in Renal Clear Cell Carcinoma

miR‑16‑2‑3p inhibits cell proliferation and migration and induces apoptosis by targeting PDPK1 in�maxillary primordium mesenchymal cells

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