PTBP1 enhances exon11a skipping in Mena pre-mRNA to promote migration and invasion in lung carcinoma cells

Li, Shuaiguang; Shen, Lianghua; Huang, Luyuan; Lei, Sijia; Cai, Xingdong; Breitzig, Mason; Zhang, Bin; Yang, Annan; Ji, Wenzuo; Huang, Meiyan; Zheng, Qi; Sun, Han; Wang, Rui

doi:10.1016/j.bbagrm.2019.04.006

Cited by 25 publications

(19 citation statements)

References 50 publications

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“…Our data revealed that PTBP1 was significantly higher in LUAD cancer tissues compared with normal human lung tissue, consistent with previous studies ( 53 ). A recent study found that PTBP1 is overexpressed in ovarian tumors and colorectal cancer ( 54 ), indicating that PTBP1 is closely associated with the pathogenesis and development of cancer.…”

Section: Discussionsupporting

confidence: 93%

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1

et al. 2022

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PurposeLung adenocarcinoma (LUAD) is the most common type of cancer and the leading cause of cancer-related death worldwide, resulting in a huge economic and social burden. MiRNA-195-5p plays crucial roles in the initiation and progression of cancer. However, the significance of the miRNA-195-5p/polypyrimidine tract-binding protein 1 (miRNA-195-5p/PTBP1) axis in the progression of lung adenocarcinoma (LUAD) remains unclear.MethodsData were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The starBase database was employed to examine the expression of miRNA-195-5p, while the Kaplan–Meier plotter, UALCAN, and Gene Expression Profiling Interactive Analysis (GEPIA) databases were utilized to analyze the tumor stage and prognostic value of miRNA and PTBP1. Quantitative reverse transcription-polymerase chain reaction assay was conducted to detect the expression levels of miRNA-195-5p in LUAD cell lines and tissues. The effects of miRNA-195-5p on cell proliferation and migration were examined using the cell growth curve, clone information, transwell assays, and wound healing assays.ResultsWe found that miRNA-195-5p was down-regulated in LUAD cancer and cell lines. Importantly, its low levels were related to the tumor stage, lymph node metastasis, and poor prognosis in LUAD. Overexpression of miR-195-5p significantly inhibited cell growth and migration promotes cell apoptosis. Further study revealed that PTBP1 is a target gene of miRNA-195-5p, and overexpression of miRNA-195-5p inhibited the progression of LUAD by inhibiting PTBP1 expression. MiRNA-195-5p expression was related to immune infiltration in lung adenocarcinoma. Moreover, PTBP1 was negatively correlated with diverse immune cell infiltration and drug sensitivity.ConclusionOur findings uncover a pivotal mechanism that miRNA-195-5p by modulate PTBP1 expression to inhibit the progression of LUAD. MiRNA-195-5p could be a novel diagnostic and prognostic molecular marker for LUAD.

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Section: Discussionsupporting

confidence: 93%

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1

et al. 2022

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“…Then we analyzed how PTBP1 regulates NR2F1 expression. Previous studies showed that PTBP1 could bind to gene promoter regions to regulate transcription 54 , or bind to the polypyrimidine regions of mRNAs to regulate post-transcriptional processes including alternative splicing 55 , 56 , mRNA decay 57 , and IRES-dependent translation 58 – 60 . We first tested the effect of PTBP1 and NAS1 on NR2F1 promoter via luciferase reporter assays and found that NR2F1 promoter activity was not obviously changed by either PTBP1 or NAS1 (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63

Liu

Zhang

et al. 2021

Nat Commun

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Disseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.

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“…PTB facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11 (Z. N. Wang et al, 2017). PTB modulates Mena exon11a skipping to promote lung cancer cells migration and invasion (S. Li et al, 2019). PTB upregulated MEIS2‐L variant to promote LN metastasis of bladder cancer and increased expression of pyruvate kinase M2 (PKM2) variant (R. Xie et al, 2019).…”

Section: Roles Of Ptb In Diseasesmentioning

confidence: 99%

PTB: Not just a polypyrimidine tract‐binding protein

Dai

Wang

Zhang

et al. 2022

Journal Cellular Physiology

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Polypyrimidine tract-binding protein (PTB), as a member of the heterogeneous nuclear ribonucleoprotein family, functions by rapidly shuttling between the nucleus and the cytoplasm. PTB is involved in the alternative splicing of pre-messenger RNA (mRNA) and almost all steps of mRNA metabolism. PTB regulation is organ-specific; brain-or muscle-specific microRNAs and long noncoding RNAs partially contribute to regulating PTB, thereby modulating many physiological and pathological processes, such as embryonic development, cell development, spermatogenesis, and neuron growth and differentiation. Previous studies have shown that PTB knockout can inhibit tumorigenesis and development. The knockout of PTB in glial cells can be reprogrammed into functional neurons, which shows great promise in the field of nerve regeneration but is controversial.

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PTBP1 enhances exon11a skipping in Mena pre-mRNA to promote migration and invasion in lung carcinoma cells

Cited by 25 publications

References 50 publications

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1

Immune-Related miRNA-195-5p Inhibits the Progression of Lung Adenocarcinoma by Targeting Polypyrimidine Tract-Binding Protein 1

Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63

PTB: Not just a polypyrimidine tract‐binding protein

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