MiR-142-5p Suppresses Tumorigenesis by Targeting PIK3CA in Non-Small Cell Lung Cancer

Wang, Zhao; Liu, Zhimin; Fang, Xiaojie; Yang, Han

doi:10.1159/000484459

Cited by 64 publications

(47 citation statements)

References 43 publications

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“…PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) [13]. Several studies have reported that PIK3R3 is abnormally overexpressed in some types of cancer, such as lung cancer, colorectal cancer, and gastric cancer [14-16].…”

Section: Introductionmentioning

confidence: 99%

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

Peng

Zhu

Yin

et al. 2018

Cell Physiol Biochem

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Background/Aims: PIK3R3 is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) which plays an essential role in the metastasis of several types of cancer. However, whether PIK3R3 can promote the metastasis of pancreatic cancer (PC) is still unclear. In this study, we characterized the role of PIK3R3 in metastasis of PC and underlying potential mechanisms. Methods: RT-PCR, western blot, immunofluorescence (IF) and immunohistochemistry (IHC) were applied to investigate the expression of genes and proteins in different cell lines and tissues. To assess the function of PIK3R3 and related mechanisms, the cells with RNAi-mediated knockdown or overexpression were used to perform a series of in vitro and in vivo assays. Results: PIK3R3 was significantly overexpressed in pancreatic cancer tissues, especially in metastatic cancer tissues, as well as in pancreatic cancer cells. Functional assays suggested that overexpression or knockdown of PIK3R3 could respectively promote or suppress the migration and invasion of PC cells in vitro and in vivo. Further mechanism related studies demonstrated that ERK1/2-ZEB1 pathway-triggered epithelial-mesenchymal transition (EMT) might be responsible for the PIK3R3-induced PC cell migration and invasion. Conclusion: PIK3R3 could promote the metastasis of PC by facilitating ZEB1 induced EMT, and could act as a potential therapeutic target to limit PC metastasis.

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Section: Introductionmentioning

confidence: 99%

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

Peng

Zhu

Yin

et al. 2018

Cell Physiol Biochem

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“…NSCLC is one of the most common malignancies that threatens human health and life (23). The major therapy methods for NSCLC include radiotherapy and chemotherapy (24), but due to resistance, the mortality rate of NSCLC remains high (25). Furthermore, the underlying mechanism by which NSCLC is modulated is not fully understood (25).…”

Section: Discussionmentioning

confidence: 99%

“…The major therapy methods for NSCLC include radiotherapy and chemotherapy (24), but due to resistance, the mortality rate of NSCLC remains high (25). Furthermore, the underlying mechanism by which NSCLC is modulated is not fully understood (25). miRNAs are key regulators of NSCLC progression and therefore may become an important therapeutic target (26).…”

Section: Discussionmentioning

confidence: 99%

High serum miR‑484 expression is associated with the diagnosis and prognosis of patients with non‑small cell lung cancer

2019

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The aim of the current study was to assess the expression and clinical significance of serum microRNA (miR)-484 in patients with non-small cell lung cancer (NSCLC). Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of miR-484 in the serum of patients with NSCLC and NSCLC cell lines. Cell counting kit-8, flow cytometry, cell migration and cell invasion assays were performed to assess the role of miR-484 in the malignant changes associated with NSCLC cells. Furthermore, to assess the diagnostic value of miR-484, receiver operating curve (ROC) analysis was performed and the clinical relevance of serum miR-484 expression in patients with NSCLC was determined. A Kaplan-Meier analysis with the log-rank test was performed to assess the overall survival rate patients. To the best of our knowledge, the current study demonstrates for the first time that serum miR-484 was increased in patients with NSCLC compared with healthy controls. Additionally, serum miR-484 was revealed to be positively associated with histological grade, lymph node metastasis, distant metastasis and clinical stage. Patients with NSCLC and high serum miR-484 levels demonstrated significantly poorer overall survival rates compared with those exhibiting lower serum miR-484 expressions. ROC analysis revealed that serum miR-484 could screen patients with NSCLC patients from healthy controls with a high sensitivity and specificity. In vitro analysis also demonstrated that miR-484 was significantly upregulated in NSCLC cell lines, including 95D and H358 cells. Furthermore, the suppression of miR-484 decreased cell proliferation, cell migration and invasion. In summary, the results of the present study demonstrated that increased serum miR-484 expression is associated with the diagnosis and prognosis of patients with NSCLC. High serum miR-484 expression is associated with the diagnosis and prognosis of patients with non-small cell lung cancer

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“…The question remains whether mutations in solid tumors, in which miR-142-3p acts predominantly as a tumor suppressor, among others targeting and downregulating TGFB1R and HMGB1 63,64 , may also have functional consequences. It was shown that miR-142-3p plays a role in different solid tumors (e.g., breast 65,66 , ovarian 67 , colorectal 68,69 , and lung cancer [70][71][72] ). Hsa-miR-142 constitutes an example showing that cancer-specific enrichment of mutations may be a strong indicator of their functional relevance for cancer.…”

Section: Hsa-mir-142mentioning

confidence: 99%

Pan-Cancer analysis of somatic mutations in miRNA genes

Urbanek-Trzeciak

Galka-Marciniak

Nawrocka

et al. 2020

Preprint

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175)miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. Here, based on analysis of the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we identified and characterized over 10,000 somatic mutations in miRNA genes and showed that some of the genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. Our results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancerdriver miRNA genes. The results published here are based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. This work was supported by research grants from the Polish National Science Centre [2016/22/A/NZ2/00184 (to P.K.) and 2015/17/N/NZ3/03629 (to M.O.U-T.)] Authors contributions MUTparticipated in conceiving the study, wrote all the scripts, performed most of the computational and statistical analyses, drafted the manuscript, prepared figures, tables, and supplementary materials; PGMparticipated in conceiving the study, discussed the study on all steps of analyses, participated in manuscript preparation, performed some analyses (3D structures); PNdiscussed the analyses on all steps of the study, performed some analyses, participated in manuscript preparation; EKperformed the sequencing experiments, critically read and corrected manuscript; SSperformed the sequencing experiments, critically read and corrected manuscript; MGprovided samples for the hsa-miR-1324 and hsa-miR-142 sequencing validation experiments, advised on hematological neoplasms and head and neck cancer, critically read and corrected manuscript; PKreceived financing, participated in conceiving the study, supervised and coordinated the study, drafted the manuscript (with MUT).

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MiR-142-5p Suppresses Tumorigenesis by Targeting PIK3CA in Non-Small Cell Lung Cancer

Cited by 64 publications

References 43 publications

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

PIK3R3 Promotes Metastasis of Pancreatic Cancer via ZEB1 Induced Epithelial-Mesenchymal Transition

High serum miR‑484 expression is associated with the diagnosis and prognosis of patients with non‑small cell lung cancer

Pan-Cancer analysis of somatic mutations in miRNA genes

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