The Esophageal Cancer and the PI3K/AKT/mTOR Signaling Regulatory microRNAs: a Novel Marker for Prognosis, and a Possible Target for Immunotherapy

Javadinia, Seyed Alireza; Shahidsales, Soodabeh; Fanipakdel, Azar; Mostafapour, Asma; Joudi‐Mashhad, Mona; Ferns, Gordon A.

doi:10.2174/1381612825666190110143258

Cited by 37 publications

(31 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data showed that SLBZ-AP Many researchers confirmed that PI3K/Akt/mTOR signaling pathway is related to a few biological activities to affect cell proliferation, survival, and migration [7,8], especially to stimulate proliferation, survival, invasion/metastasis, and metabolic reprogramming and suppress autophagy, which is involved in possible mechanisms of oncogenic transformation [9]. PI3K/Akt/mTOR signaling pathway is commonly activated and suppression of its activation may inhibit cells proliferation and metastasis in cancers of the lung [10,11,50], colorectal [51,52], esophagus [53], breast [54][55][56], liver [57,58], and kidney [59,60], which has been considered a promising therapeutic target. Whether the PI3K/Akt/mTOR signaling pathway involved in SLBZ-AP affects BMLC was further explored in our study, results of which indicated that the mRNA and protein expression of AKT, mTOR, P70S6, and VEGF as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF was significantly increased in the marrow of tibia from BMLC mice.…”

Section: Discussionmentioning

confidence: 93%

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

Feng

Han

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Shenling Baizhu additive powder (SLBZ-AP), a formulation of a variety of natural medicinal plants, has clinical efficacy in treating cancers in previous studies. We explored the effect of SLBZ-AP in bone metastasis of lung cancer (BMLC) mice, and the possible mechanism involved was further investigated in the present study. Mice model of BMLC was made and treated with SLBZ-AP. Pain behavioral tests were performed to explore the effect on BMLC-induced pain in mice. TUNEL staining was used to investigate apoptosis. The mRNA expression of markers in the PI3K/Akt/mTOR pathway was measured by qPCR, and protein expression was detected by western blotting and immunohistochemistry analysis. SLBZ-AP relieved BMLC-induced pain and prolonged animals’ survival, promoted cell apoptosis in the marrow from the tibia of BMLC mice, and inhibited mRNA and protein expression of AKT, mTOR, P70S6, and VEGF, as well as protein expression of p-AKT, p-mTOR, p-P70S6, and VEGF upregulation in the marrow of tibia induced by BMLC, an effect which was similar to rapamycin. Our results suggested that SLBZ-AP may have antinociceptive effect and prolong survival of BMLC mice at least partially by inhibiting cell proliferation and promoting apoptosis through the PI3K/Akt/mTOR signaling pathway. SLBZ-AP may be a potential candidate for BMLC therapy.

show abstract

Section: Discussionmentioning

confidence: 93%

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

Feng

Han

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Membrane kinases including epidermal growth factor receptor (EGFR) are activated by external growth factors, which initiate receptor dimerization and subsequent events to activate these intracellular pathways. AKT has multiple targets to modulate a variety of proliferative and antiproliferative signaling processes, such as survival, apoptosis, angiogenesis, cell cycle, cell-cycle energy, and DNA repair [17][18][19][20][21][22]. Additionally, Lianghai Wang et al showed that the elevation of SOX9 inhibits the transcription of miR-203a by binding to the miR-203a promoter, thereby abolishing miR-203a-mediated impediment of PI3K/AKT/ mTOR pathway [23].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma

Kong

Shang

Diao

et al. 2021

Journal of Oncology

View full text Add to dashboard Cite

Objective. Esophageal carcinoma (ESCA) is a common malignant gastrointestinal tumor. The abnormal expression of NOLC1 is involved in the tumorigenesis of various human tumors, whereas the function and mechanism of NOLC1 in ESCA remain unclear. In this study, we explored the relationship between NOLC1 and poor prognosis of ESCA, and its role and mechanism in the occurrence of ESCA. Methods. The NOLC1 expression in ESCA tissues and cell lines was determined by qRT-PCR, immunohistochemistry, or western blot. The Kaplan–Meier method was conducted to estimate the overall survival. Cox regression analysis was carried out to examine the association between patient characteristics and prognosis. A recombined lentiviral vector containing NOLC1 was applied for transfecting ESCA cells (Eca109 and TE-13) and established a stable cell line with low NOLC1 expression or high NOLC1 expression, in the absence or presence of PI3K inhibitor (LY294002) treatment. Cell proliferation, apoptosis rate, invasion ability, migration ability, and PI3K/AKT pathway were detected by CCK8 assay, flow cytometry, Transwell assay, wound-healing assay, and western blot. Results. NOLC1 overexpression was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared with adjacent normal tissues and normal esophageal cell line HEEC. NOLC1 overexpression was markedly associated with bigger tumor size, lymph node metastasis, and advanced TNM stage. Patients with NOLC1 overexpression have shorter overall survival than that of those with low NOLC1 expression. NOLC1 overexpression was considered to be an independent poor prognostic factor affecting overall survival. NOLC1 knockdown inhibited proliferation, migration, invasion, and cyclin B1 expression and promoted the apoptosis and cleaved-caspase-3 expression of Eca109 and TE-13 cells. NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of ESCA cells via activating PI3K/AKT pathway. Rescue experiments showed that PI3K inhibitor (LY294002) could reverse the phenomenon caused by NOLC1 overexpression. Conclusion. NOLC1 may be a marker for poor prognosis. It can participate in the occurrence and development of ESCA via the PI3K/AKT pathway.

show abstract

“…These signaling had crucial roles in cancer cells. For example, PI3K/AKT pathway was activated in EC samples ( Javadinia et al, 2018 ). Using specific inhibitors targeting this pathway significantly inhibited cell proliferation, enhancing apoptosis in EC cells ( Shi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of a Nine-MicroRNA-Based Signature to Predict the Overall Survival of Esophageal Cancer Patients

Zhang

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

BackgroundEsophageal cancer (EC) is a common malignant tumor. MicroRNAs (miRNAs) play a key role in the occurrence and metastasis and are closely related to the prognosis of EC. Therefore, it will provide a powerful tool to predict the overall survival (OS) of EC patients based on miRNAs expression in EC tissues and blood samples.MethodsFive independent databases, TCGA, GSE106817, GSE113486, GSE122497, and GSE112264, were used to construct nine-miRna signature and nomograms for prognosis. The bioinformatics analysis was used to predict the enrichment pathways of targets.ResultsA total of 132 overexpressed miRNAs and 23 suppressed miRNAs showed significant differential expression in both EC serum and tissue samples compared with normal samples. We also showed that nine miRNAs were related to the prognosis of EC. Higher levels of miR-15a-5p, miR-92a-3p, miR-92a-1-5p, miR-590-5p, miR-324-5p, miR-25-3p, miR-181b-5p, miR-421, and miR-93-5p were correlated to the shorter survival time in patients with EC. In addition, we constructed a risk prediction model based on the levels of nine differentially expressed miRNAs (DEMs) and found that the OS time of EC patients with high-risk score was shorter than that of EC patients with low-risk score. Furthermore, our results showed that the risk prediction scores of EC samples were higher than those of normal samples. Finally, the area under the curve (AUC) was used to analyze the risk characteristics of EC and normal controls. By calculating the AUC and the calibration curve, the RNA signature showed a good performance. Bioinformatics analysis showed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling. Finally, 14 messenger RNAs (mRNAs) were identified as hub targets of nine miRNAs, including BTRC, SIAH1, RNF138, CDC27, NEDD4L, MKRN1, RLIM, FBXO11, RNF34, MYLIP, FBXW7, RNF4, UBE3C, and RNF111. TCGA dataset validation showed that these hub targets were significantly differently expressed in EC tissues compared with normal samples.ConclusionWe have constructed maps and nomograms of nine-miRna risk signals associated with EC prognosis. Bioinformatics analysis revealed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling, in EC. We think that this study will provide clinicians with an effective decision-making tool.

show abstract

The Esophageal Cancer and the PI3K/AKT/mTOR Signaling Regulatory microRNAs: a Novel Marker for Prognosis, and a Possible Target for Immunotherapy

Cited by 37 publications

References 69 publications

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

Antinociceptive Effects of Shenling Baizhu through PI3K‐Akt‐mTOR Signaling Pathway in a Mouse Model of Bone Metastasis with Small‐Cell Lung Cancer

Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma

Construction of a Nine-MicroRNA-Based Signature to Predict the Overall Survival of Esophageal Cancer Patients

Contact Info

Product

Resources

About