miR‑10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway

Huang, Tonghai; Ren, Kangqi; Ding, Guanggui; Yang, Lin; Wen, Yuanyuan; Peng, Bin; Wang, Guangsuo; Zheng, Wei

doi:10.3892/or.2020.7547

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…PIK3CA locates on chromosome 3 and encodes the p110α catalytic subunit of PI3K, which can enhance cell activity and tumour formation via positively regulating PI3K/Akt activity [9]. PIK3CA regulates the generation of phosphatidylinositol triphosphate to activate Akt/PKB kinase.…”

Section: Discussionmentioning

confidence: 99%

“…As is widely known, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is involved in physiological processes underlying a variety of biological reactions, including inflammation and apoptosis [7,8]. As a target gene of miR-10a, the PI3K p100 catalytic subunit α (PIK3CA) plays a critical role in the cisplatin resistance of lung adenocarcinoma circulating tumor cells via the in PI3K/Akt pathway [9]. Many studies have reported that hypoxia-reoxygenation (H/R) injury can activate the PI3K/Akt pathway to protect renal tubular epithelial cells [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression

Zhang³

et al. 2020

BMC Nephrol

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Background: To investigate the effect of miR-10a on renal tissues with ischemia reperfusion (I/R) injury in rats and to explore the underlying mechanisms of the effect of miR-10a on hypoxia-reoxygenation in HK-2 cells. Methods: MiR-10a level was measured in the renal tissues of rats with I/R rats using RT-PCR. In order to research the role of miR-10a in renal tissues, an miR-10 agonist and an miR-10a antagonist were used to treat I/R-injured rats. Levels of serum creatinine and blood urea nitrogen, renal histopathology, and levels of cell apoptosis were analyzed separately in renal tissues from the rats. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blotting. In addition, HK-2 cells were cultured in order to study the mechanism of action of miR-10a in the hypoxia-reoxygenation model being studied. Finally, the dual luciferase reporter gene assay was used to confirm that the PI3K p100 catalytic subunit α (PIK3CA) gene was targeted by miR-10a. Results: After renal I/R injury in rats, miR-10a expression increased significantly (p < 0.05). Injection of miR-10a agonist significantly aggravated the renal injury and raised the level of cell apoptosis in the renal tissues of I/Rinjured rats (p < 0.05). However, administration of miR-10a antagonist led to obvious improvement of the renal injury, decreased renal cell apoptosis, and inhibited PI3K/Akt pathway activity (p < 0.05). In in vitro experiments, the negative relationship between PIK3CA and miR-10a levels was confirmed. Furthermore, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased cell apoptosis via up-regulation of the PI3K/Akt pathway (p < 0.05). Conclusion: The aggravation of renal I/R injury by miR-10a was associated with a decrease in the activity of PIK3CA/PI3K/Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression

Zhang³

et al. 2020

BMC Nephrol

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“…MiR-10a expression promotes the metastatic behavior of pancreatic tumor cells and its repression is sufficient to inhibit invasion and metastasis formation [ 36 ]. The downregulation of miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth [ 37 ] and increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway [ 38 ]. MiR-26a can function not only as tumor suppressor but also as an oncogenic miRNA; its function is tumor type-specific and highly dependent on its targets in different cancer cells.…”

Section: Resultsmentioning

confidence: 99%

GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model

Gerovska

García-Gallastegi

Crende

et al. 2021

IJMS

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Cancer is a phenomenon broadly related to ageing in various ways such as cell cycle deregulation, metabolic defects or telomerases dysfunction as principal processes. Although the tumor cell is the main actor in cancer progression, it is not the only element of the disease. Cells and the matrix surrounding the tumor, called the tumor microenvironment (TME), play key roles in cancer progression. Phenotypic changes of the TME are indispensable for disease progression and a few of these transformations are produced by epigenetic changes including miRNA dysregulation. In this study, we found that a specific group of miRNAs in the liver TME produced by colon cancer called geromiRs, which are miRNAs related to the ageing process, are significantly downregulated. The three principal cell types involved in the liver TME, namely, liver sinusoidal endothelial cells, hepatic stellate (Ito) cells and Kupffer cells, were isolated from a murine hepatic metastasis model, and the miRNA and gene expression profiles were studied. From the 115 geromiRs and their associated hallmarks of aging, which we compiled from the literature, 75 were represented in the used microarrays, 26 out of them were downregulated in the TME cells during colon cancer colonization of the liver, and none of them were upregulated. The histone modification hallmark of the downregulated geromiRs is significantly enriched with the geromiRs miR-15a, miR-16, miR-26a, miR-29a, miR-29b and miR-29c. We built a network of all of the geromiRs downregulated in the TME cells and their gene targets from the MirTarBase database, and we analyzed the expression of these geromiR gene targets in the TME. We found that Cercam and Spsb4, identified as prognostic markers in a few cancer types, are associated with downregulated geromiRs and are upregulated in the TME cells.

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“…et al, 2016 ). To contribute to Akt activation and DDP-resistance, PI3K also is targeted by miR-10a ( Huang T. et al, 2020 ). In the same way, two downstream effectors of the PI3K/Akt pathway are also regulated by miRs.…”

Section: Micrornas Involved In Ddp-chemoresistancementioning

confidence: 99%

Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review

Loren

Saavedra

et al. 2022

Front. Pharmacol.

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Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both in vitro and in vivo human models.

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miR‑10a increases the cisplatin resistance of lung adenocarcinoma circulating tumor cells via targeting PIK3CA in the PI3K/Akt pathway

Cited by 17 publications

References 42 publications

miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression

miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression

GeromiRs Are Downregulated in the Tumor Microenvironment during Colon Cancer Colonization of the Liver in a Murine Metastasis Model

Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review

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