miR-433 suppresses tumor progression via Smad2 in non-small cell lung cancer

Li, Jianing; Meng, Chen; Yu, Bu Chin

doi:10.1016/j.prp.2019.152591

Cited by 35 publications

(36 citation statements)

References 24 publications

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“…Aberrant expression of miR-433-3p has been observed in multiple human cancer types including NSCLC (30). In our study, miR-433-3p overexpression led to obvious decreases in NSCLC cell proliferation, migration, and invasion in vitro and hindered tumor growth in vivo.…”

Section: Discussionsupporting

confidence: 56%

“…According to Starbase3.0, OSER1-AS1 harbors base pairs complementary to miR-433-3p (Fig. 3B), and the latter miRNA was chosen for subsequent experimental identification because of its role as a cancer inhibitor during NSCLC progression (30). Luciferase reporter and RIP assays were performed to validate the true interaction between OSER1-AS1 and miR-433-3p in NSCLC cells.…”

Section: Oser1-as1 Expression (N=53) --------------------------------mentioning

confidence: 99%

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Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

et al. 2020

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OSER1 antisense RNA 1 (OSER1-AS1), a long noncoding RNA, has been well studied in the context of hepatocellular carcinoma. However, its expression status, specific functions, and tumorigenic mechanism in non-small cell lung cancer (NSCLC) remain uninvestigated. Hence, this study aimed to assess OSER1-AS1 expression, test the malignancy-related biological functions of OSER1-AS1, and illustrate how they affect NSCLC progression. OSER1-AS1 expression in NSCLC was measured by reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8 assay, flow cytometry, cell migration and invasion assay, and tumor xenograft assay were performed to analyze the effects of OSER1-AS1 on the malignant phenotypes of NSCLC cells. Bioinformatics prediction with luciferase reporter and RNA immunoprecipitation assays were performed to determine the interaction between OSER1-AS1 and microRNA-433-3p (miR-433-3p). OSER1-AS1 was strongly expressed in NSCLC tissues and cell lines. Enhanced OSER1-AS1 expression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in patients with NSCLC. Patients with NSCLC exhibiting high OSER1-AS1 expression had shorter overall survival than those exhibiting low OSER1-AS1 expression. Functionally, a reduction in OSER1-AS1 expression led to significant decreases in NSCLC cell proliferation, migration, and invasion as well as an increase in cell apoptosis in vivo. OSER1-AS1 knockdown suppressed the tumorigenic ability of NSCLC cells in vivo. Mechanistically, OSER1-AS1 acts as a competing endogenous RNA (ceRNA) in NSCLC cells by sponging miR-433-3p and thereby increasing the expression of mothers against decapentaplegic homolog 2 (Smad2). Finally, restoration experiments revealed that the suppression of miR-433-3p and restoration of Smad2 both counteracted the suppressive effects of OSER1-AS1 depletion in NSCLC cells. Our findings illustrate the biological importance of the OSER1-AS1/miR-433-3p/Smad2 pathway in NSCLC progression and offer a novel perspective regarding the identification of effective therapeutic and diagnostic targets.

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Section: Discussionsupporting

confidence: 56%

Section: Oser1-as1 Expression (N=53) --------------------------------mentioning

confidence: 99%

Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

et al. 2020

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Section: Introductionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) had widely been reported to regulate NSCLC progression [ 24 ]. For example, overexpression of miR-433 inhibited the development of NSCLC by targeting Smad2 [ 24 ] and miR-421 played an oncogenic role in NSCLC progression [ 25 ]. Among all the miRNAs, let-7 miRNA served as a tumor suppressor in multiple cancers [ 26 – 28 ], such as bladder cancer [ 27 ], ovarian cancer [ 26 ] and NSCLC [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Hong

Xue

Jiang

et al. 2020

J Exp Clin Cancer Res

251

194

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Background Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment. Methods Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay. Results Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8 + T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8 + T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8 + T cells in the co-culturing system. Conclusion Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8 + T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.

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“…Previous studies have shown that miR-375 and miR-433 have been shown to be differentially expressed in many cancers and involved in the regulation of cancer progression. 20,21 Moreover, the results of Xu et al and Shi et al suggested that miR-375 and miR-433 expression were decreased in ESCC. 22,23 Therefore, miR-375 and miR-433 might function as the tumor suppressor in ESCC.…”

Section: Discussionmentioning

confidence: 99%

<p>Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433</p>

Cheng

Jiang

Song

et al. 2020

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Background: Circular RNAs (circRNAs) are critical regulators of many diseases, including esophageal squamous cell carcinoma (ESCC). A recent study has shown that circLPAR3 is highly expressed in ESCC, but its role and mechanism in ESCC are still unclear. Methods: The expression levels of circLPAR3, microRNA-375 (miR-375), miR-433, and high-mobility group box 1 (HMGB1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular characteristic and localization of circLPAR3 were identified by Ribonuclease R (RNase R) and nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were tested by transwell assay. Moreover, Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related protein, as well as the HMGB1 protein. Besides, mice xenograft models were constructed to assess the effect of circLPAR3 on ESCC tumor growth in vivo. In addition, dual-luciferase reporter and RNA pull-down assays were used to identify the mechanism of circLPAR3. Results: CircLPAR3 was upregulated in ESCC tissues and cells, and its high expression was related to the poor prognosis of ESCC patients. CircLPAR3 was a stable cyclic transcript, mainly located in the cytoplasm, and its knockdown hindered the proliferation, migration and invasion of ESCC cells and inhibited ESCC tumor growth in vivo. MiR-375/miR-433 could be sponged by circLPAR3, and their inhibitors could reverse the suppression effect of silenced circLPAR3 on ESCC progression. HMGB1 could be targeted by miR-375/miR-433, and its overexpression also could invert the inhibition effect of circLPAR3 knockdown on ESCC progression. Conclusion: CircLPAR3 might play an oncogenic role in ESCC through sponging miR-375/ miR-433 to promote HMGB1 expression, which might provide a theoretical basis for circLPAR3 to become a biomarker for ESCC therapy.

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miR-433 suppresses tumor progression via Smad2 in non-small cell lung cancer

Cited by 35 publications

References 24 publications

Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

Long noncoding RNA OSER1‑AS1 promotes the malignant properties of non‑small cell lung cancer by sponging microRNA‑433‑3p and thereby increasing Smad2 expression

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

<p>Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433</p>

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