LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP

Weng, Lei; Qiu, Kejie; Gao, Weijing; Shi, Chunbo; Shu, Fen

doi:10.1186/s12890-020-01240-5

Cited by 35 publications

(32 citation statements)

References 27 publications

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“…Mechanically, circ_0010235 possessed several miRNA response elements in the primary sequence. Among these candidate miRNAs, miR-197-3p was enormously raised in plasma of lung cancer patients and tissues of NSCLC patients [ 22 , 23 ], and plasma miR-197-3p was involved with NSCLC tumour stage and metastasis [ 22 ]; miR-433-3p was downregulated in different NSCLC cell lines [ 24 ]; miR-338-3p was a relatively better-studied miRNA in lung cancers through serving as tumour suppressor. Therefore, miR-338-3p was chose to be candidate target for circ_0010235, and this connection was further identified using dual-luciferase reporter assay and Ago2 RIP assay.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Zhu

et al. 2021

Annals of Medicine

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Background Circular RNA microarray analysis showed hsa_circ_0010235 (circ_0010235) was highly upregulated in non-small-cell lung cancer (NSCLC) patients; however, its role in carcinogenesis and development of NSCLC cells was unrevealed. Here, we intended to investigate role and mechanism of circ_0010235 in NSCLC proliferation, migration and invasion. Methods and results Expression of circ_0010235, microRNA (miR)-338-3p and kinesin family member 2A (KIF2A) was detected by quantitative real-time PCR, western blotting and immunohistochemistry (IHC). Cell progression was measured by cell-counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) assay, flow cytometry, transwell assay, western blotting, IHC and xenograft experiment. The relationship among circ_0010235, miR-338-3p and KIF2A was determined by dual-luciferase reporter assay, RNA immunoprecipitation and Pearson’s correlation analysis. Expression of circ_0010235 was increased in human NSCLC tissues and cells, accompanied with miR-338-3p downregulation and KIF2A upregulation. Essentially, circ_0010235 could sponge miR-338-3p via target binding, and miR-338-3p downstream targeted KIF2A. Functionally, exhaustion of circ_0010235 induced apoptosis rate of NSCLC cells and curbed cell viability, EdU incorporation, migration rate and invasion rate, accompanied with higher E-cadherin and lower N-cadherin expression. Additionally, re-expression of miR-338-3p prompted above similar effects in NSCLC cells in vitro . Contrarily, miR-338-3p blockage partially counteract the effects of circ_0010235 exhaustion; plus, restoration of KIF2A could attenuate miR-338-3p role, as well. Notably, interfering circ_0010235 delayed tumour growth of NSCLC cells by promoting miR-338-3p and E-cadherin expression, and depressing KIF2A, ki-67 and N-cadherin expression. Conclusions circ_0010235 could be a novel identified oncogenic circRNA in NSCLC, and targeting miR-338-3p/KIF2A axis was one regulatory mechanism underlying circ_0010235. KEY MESSAGE Circ_0010235 was an upregulated circRNA in NSCLC patients and cells. Interfering circ_0010235 restrained NSCLC cell proliferation and metastasis in vitro and in vivo . miR-338-3p per se suppressed NSCLC in vitro and its downregulation diminished the tumour-suppressive role of circ_0010235 blockage in NSCLC cells. miR-338-3p could downstream target KIF2A and be sponged by circ_0010235.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Zhu

et al. 2021

Annals of Medicine

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“…The present study reported that exosomal miR-433 expression was lower in plasma of patients with chemotherapy-resistant NSCLC compared with in plasma of patients with chemotherapy-sensitive NSCLC and in normal serum, and miR-433 expression was significantly negatively associated large tumor size, advanced TNM stage, distant metastasis and a poor prognosis in patients with NSCLC. Notably, Weng et al ( 30 ) also reported that PCGEM1 prostate-specific transcript (PCGEM1) was highly expressed in NSCLC cells, while miR-433-3p was lowly expressed in NSCLC cells. PCGEM1 silencing or miR-433-3p overexpression inhibit cell proliferation, migration and invasion, but accelerate apoptosis in NSCLC cells ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, Weng et al ( 30 ) also reported that PCGEM1 prostate-specific transcript (PCGEM1) was highly expressed in NSCLC cells, while miR-433-3p was lowly expressed in NSCLC cells. PCGEM1 silencing or miR-433-3p overexpression inhibit cell proliferation, migration and invasion, but accelerate apoptosis in NSCLC cells ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer

et al. 2021

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Tumor-derived exosomal microRNAs (miRNAs/miRs) serve a vital biological role in tumorigenesis and development, but the effects and underlying mechanisms remain unclear. To explore the impact of exosomal miR-433 in non-small cell lung cancer (NSCLC) and understand its mechanism of action in NSCLC progression, the present study isolated the exosomes from the plasma of patients with NSCLC after chemotherapy and found that miR-433 expression was lower in plasma of patients with resistant NSCLC compared with in plasma of patients with sensitive NSCLC and in normal serum. Additionally, miR-433 expression was markedly negatively associated with a large tumor size, distant metastasis, advanced TNM stage and a poor prognosis in patients with NSCLC. miR-433 inhibited tumor growth by blocking the cell cycle in vitro and in vivo , as well as by promoting apoptosis and T-cell infiltration in the tumor microenvironment. Additionally, miR-433 inhibited chemoresistance to cisplatin by regulating DNA damage. Moreover, miR-433 inactivated the WNT/β-catenin signaling pathway by targeting transmembrane p24 trafficking protein 5 in NSCLC. Overall, the current findings may provide a potential prognostic biomarker and therapeutic target for patients with NSCLC.

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“…The expression levels of PCGEM1 in NSCLC tissues are significantly higher than those in adjacent normal tissues. PCGEM1 expression have also been quantified in NSCLC cell lines and is notably upregulated compared to that in normal control cells ( 31 – 33 ). Moreover, PCGEM1 expression is closely associated with TNM stage (P=0.020) and lymph node metastasis (P=0.034) ( 33 ).…”

Section: Association Between Pcgem1 and Clinicopathological Features ...mentioning

confidence: 99%

LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility

Zheng

et al. 2022

Front. Oncol.

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As novel members of the noncoding RNA family, long noncoding RNAs (lncRNAs) have been widely reported to function as powerful regulators in gene expression processes, including chromosome remodeling, transcription interference and posttranscriptional modification. With the rapid development of metagenomic sequencing, numerous studies have indicated that the dysregulation of lncRNAs is closely associated with diverse human diseases, especially cancers. Prostate Gene Expression Marker 1 (PCGEM1), a recently identified lncRNA, has been reported to play a crucial role in the initiation and progression of multiple tumors by interacting with pivotal regulators of tumor-related signaling pathways. In this review, we will retrospectively review the recent studies of the expression of lncRNA PCGEM1 in human cancers and comprehensively describe the underlying regulatory mechanism by which PCGEM1 functions in tumors. More importantly, based on the relationship between PCGEM1 and cancers, the potential application of PCGEM1 in clinical diagnosis, prognosis and therapeutic treatment will also be highlighted.

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LncRNA PCGEM1 accelerates non-small cell lung cancer progression via sponging miR-433-3p to upregulate WTAP

Cited by 35 publications

References 27 publications

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Exosome‑derived microRNA‑433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non‑small cell lung cancer

LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility

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