LncRNA OXCT1-AS1 promotes the proliferation of non-small cell lung cancer cells by targeting the miR-195/CCNE1 axis

Wang, Dapeng; Chen, Ying; Song, Xue; Wu, Shuang; Zhang, Na; Zheng, Fei; Yang, Guangrun

doi:10.21037/tcr-22-855

Cited by 5 publications

(5 citation statements)

References 35 publications

(42 reference statements)

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“…LncRNAs, with a length over 200 nt and no protein-coding potential, are differentially expressed and exert pivotal roles in modulating cellular activities in diverse carcinomas (10)(11)(12). For examples, lncRNA OXCT1-AS1 could boost proliferation of NSCLC cells through targeting miR-195/CCNE1 axis (13); lncRNA B4GALT1-AS1 accelerates NSCLC growth via elevating ZEB1 level via sponging miR-144-3p (14). Among these lncRNAs, HOXD cluster antisense RNA 2 (HOXD-AS2) is a demonstrated oncogenic lncRNA in human carcinomas.…”

Section: Introductionmentioning

confidence: 99%

LncRNA HOXD-AS2 regulates miR-3681-5p/DCP1A axis to promote the progression of non-small cell lung cancer

Zhang¹,

Ma²

2023

J Thorac Dis

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Background: Non-small cell lung cancer (NSCLC) is the most common malignancy in lung cancer, with a low survival rate and unfavorable prognosis. Dysregulated long non-coding RNAs (lncRNAs) play vital functions in tumor progression. This study intended to probe the expression pattern and function of HOXD-AS2 in NSCLC.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the expression of HOXD-AS2, miR-3681-5p, CCR1, mRNA-decapping enzyme 1A (DCP1A), and PPP3R1.Cell viability, migration, and invasion were separately examined via 3-(4,5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide (MTT) and transwell experiments. Luciferase reporter assay was conducted to evaluate the binding of miR-3681-5p with HOXD-AS2 or DCP1A. Protein expression of DCP1A was assessed via Western blot. NSCLC animal models were constructed through injection of H1975 cells transfected with lentivirus (LV)-sh-HOXD-AS2 into nude mice, followed by hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) analysis.Results: In this study, HOXD-AS2 was upregulated in NSCLC tissues and cells, and high HOXD-AS2 predicted short overall survival (OS). Downregulation of HOXD-AS2 could impair the proliferation, migration, and invasion abilities of H1975 and A549 cells. MiR-3681-5p was shown to bind with HOXD-AS2 and be lowly expressed in NSCLC. Suppression of miR-3681-5p could abolish the inhibitory effect of HOXD-AS2 silencing on proliferation, migration, and invasion. DCP1A was screened as the target of miR-3681-5p and its overexpression could rescue miR-3681-5p upregulation-repressed proliferation, migration, and invasion activities. Moreover, animal experiments affirmed that HOXD-AS2 promoted tumor growth in vivo.Conclusions: HOXD-AS2 modulates the miR-3681-5p/DCP1A axis to boost the progression of NSCLC, which founds the basis of HOXD-AS2 as a new diagnostic biomarker and molecular target for NSCLC therapy.

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Section: Introductionmentioning

confidence: 99%

LncRNA HOXD-AS2 regulates miR-3681-5p/DCP1A axis to promote the progression of non-small cell lung cancer

Zhang¹,

Ma²

2023

J Thorac Dis

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“…Evidence on the functional role of miR-195 modulating cell cycle progression has been widely documented in distinct biological contexts, including the heart 56 , 75 , 76 , the liver 43 , 46 , 77 , 78 and the lungs 79 – 83 . Multiple cell cycle regulators such as Check1 75 , 79 , Cnne1 77 , Cdk4 77 , Ccnd1 84 and Ccnd3 77 , 81 have been described as miR-195 direct targets. We provide herein evidences that miR-195b deficiency distinctly impaired cell cycle regulators in distinct tissues.…”

Section: Discussionmentioning

confidence: 99%

miR-195b is required for proper cellular homeostasis in the elderly

Muñoz-Gallardo,

Garcia-Padilla,

Vicente-Garcia

et al. 2024

Sci Rep

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Over the last decade we have witnessed an increasing number of studies revealing the functional role of non-coding RNAs in a multitude of biological processes, including cellular homeostasis, proliferation and differentiation. Impaired expression of non-coding RNAs can cause distinct pathological conditions, including herein those affecting the gastrointestinal and cardiorespiratory systems, respectively. miR-15/miR-16/miR-195 family members have been broadly implicated in multiple biological processes, including regulation of cell proliferation, apoptosis and metabolism within distinct tissues, such as heart, liver and lungs. While the functional contribution of miR-195a has been reported in multiple biological contexts, the role of miR-195b remains unexplored. In this study we dissected the functional role of miR-195b by generating CRISPR-Cas9 gene edited miR-195b deficient mice. Our results demonstrate that miR-195b is dispensable for embryonic development. miR-195b−/− mice are fertile and displayed no gross anatomical and/or morphological defects. Mechanistically, cell cycle regulation, metabolism and oxidative stress markers are distinctly impaired in the heart, liver and lungs of aged mice, a condition that is not overtly observed at midlife. The lack of overt functional disarray during embryonic development and early adulthood might be due to temporal and tissue-specific compensatory mechanisms driven by selective upregulation miR-15/miR-16/miR-195 family members. Overall, our data demonstrated that miR-195b is dispensable for embryonic development and adulthood but is required for cellular homeostasis in the elderly.

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“…Recently, several lncRNAs have been reported to be closely associated with NSCLC progression [12,28]. For example, the lncRNAs PLAC2 [29], NUBE2R2-AS1 [30], and OXCT1-AS1 [31], which are upregulated in NSCLC, promote tumor oncogenicity. Conversely, the lncRNAs HAR1A [32], LSAMP-1 [33], and LINC00174 [34] were underexpressed in NSCLC and inhibited cancer aggressiveness.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation

Huang

Xiao

Tong

2023

Aging

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The role of the majority of long noncoding RNAs (lncRNAs) in the progression of nonsmall-cell lung cancer (NSCLC) remains elusive, despite their potential value, thus warranting in-depth studies. For example, detailed functions of the lncRNA POU6F2 antisense RNA 2 (POU6F2-AS2) in NSCLC are unknown. Herein, we investigated the expression status of POU6F2-AS2 in NSCLC. Furthermore, we systematically delineated the biological roles of POU6F2-AS2 in NSCLC alongside its downstream molecular events. We measured the expression levels of POU6F2-AS2 using quantitative real-time polymerase chain reaction and performed a series of functional experiments to address its regulatory effects in NSCLC cells. Using bioinformatic platforms, RNA immunoprecipitation, luciferase reporter assays, and rescue experiments, we investigated the potential mechanisms of POU6F2-AS2 in NSCLC. Subsequently, we confirmed the remarkable overexpression of POU6F2-AS2 in NSCLC using The Cancer Genome Atlas database and our own cohort. Functionally, inhibiting POU6F2-AS2 decreased NSCLC cell proliferation, colony formation, and motility, whereas POU6F2-AS2 overexpression exhibited contrasting effects. Mechanistically, POU6F2-AS2 acts as an endogenous decoy for microRNA-125b-5p (miR-125b-5p) in NSCLC that causes the overexpression of the E2F transcription factor 3 (E2F3). Moreover, suppressing miR-125b-5p or increasing E2F3 expression levels sufficiently recovered the anticarcinostatic activities in NSCLC induced by POU6F2-AS2 silencing. Thus, POU6F2-AS2 aggravates the oncogenicity of NSCLC by targeting the miR-125b-5p/E2F3 axis. Our findings suggest that POU6F2-AS2 is a novel therapeutic target for NSCLC.

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LncRNA OXCT1-AS1 promotes the proliferation of non-small cell lung cancer cells by targeting the miR-195/CCNE1 axis

Cited by 5 publications

References 35 publications

LncRNA HOXD-AS2 regulates miR-3681-5p/DCP1A axis to promote the progression of non-small cell lung cancer

LncRNA HOXD-AS2 regulates miR-3681-5p/DCP1A axis to promote the progression of non-small cell lung cancer

miR-195b is required for proper cellular homeostasis in the elderly

Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation

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