Down-regulation of MBNL1-AS1 contributes to tumorigenesis of NSCLC via sponging miR-135a-5p

Cao, Gang; Tan, Bing; Wei, Shanzhen; Shen, Wenyi; Wang, Xiang; Chu, Yiting; Tao, Rong; Gao, Chao

doi:10.1016/j.biopha.2020.109856

Cited by 19 publications

(23 citation statements)

References 25 publications

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“…The results indicated that expression of MBNL1-AS1 markedly decreased in breast cancer and high-metastatic BC cell lines, which wasin line with the studies revealed that MBNL1-AS1 levels were down-regulated incolorectal cancer,NSCLC,and bladder cancer. (26)(27)(28)(29)(30).Thesedemonstrated that MBNL1-AS1 mightbe a reliable biological marker to diagnose BC.The clinical signi cance of MBNL1-AS1 still needs to be further veri ed in moresamples for the limitations of the present study. Moreover, MBNL1-AS1 inhibited the proliferation and stemness of breast cancercells in vitro and inhibited the tumorigenesis of breast cancer cells in vivo was demonstrated by these results of gain-or loss of-function studies.These results indicated that MBNL1-AS1 played antioncogenic roles in BC.…”

Section: Discussionmentioning

confidence: 75%

LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer Through MBNL1-AS1/ZFP36/CENPA Axis

Ding

Duan

et al. 2021

Preprint

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Background: Emerging studies suggested the notion that long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast cancer (BC).Methods: In the present research, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the Centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and Fluorescence in situ hybridization (FISH) were conducted to detect the mechanism.Results: The results revealed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. Conclusions: We elucidated a new mechanism for how MBNL1-AS1 regulated the phenotype of BC and targeting the MBNL1-AS1/ZFP36/CENPA axis might serve as therapeutic targets for BC patients.

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Section: Discussionmentioning

confidence: 75%

LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer Through MBNL1-AS1/ZFP36/CENPA Axis

Ding

Duan

et al. 2021

Preprint

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“…LncRNAs play significant roles in the progression of PCa. MBNL1-AS1 is a newly discovered lncRNA in recent years, which has been reported as a tumor suppressor in several cancers [ 11 , 12 ]. Firstly, the expression of MBNL1-AS1 in tissue samples of patients with PCa was analyzed by using StarBase v3.0 project.…”

Section: Resultsmentioning

confidence: 99%

“…LncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) is a newly discovered lncRNA in recent years. Based on emerging research, downregulation of MBNL1-AS1 contributes to tumorigenesis of non-small cell lung cancer by promoting cell proliferation, invasion, and migration via sponging miR-135a-5p [ 11 ]. Emerging evidence supports that MBNL1-AS1 inhibits cell proliferation and intensifies cell apoptosis in bladder cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling

Ding

et al. 2021

Bioengineered

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The present study aimed to investigate the role and underlying mechanisms of long non-coding RNA (lncRNA) muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in the progression of Prostate cancer (PCa). MBNL1-AS1 and microRNA (miR)-181a-5p expression in PCa tissues and several human PCa cell lines were analyzed, respectively, using StarBasev3.0 project and RT-qPCR assay. After MBNL1-AS1 overexpression, cell proliferation, invasion and migration were, respectively, evaluated using CCK-8, colony formation, transwell and wound healing assays. Dual luciferase assay were used for analysis of the interactions among MBNL1-AS1, miR-181a-5p, and phosphatase and tensin homolog (PTEN). Subsequently, the expression of PTEN and proteins in PI3K/AKT/mTOR signaling was examined using western blot analysis after transfection with miR-181a-5p mimic. The rescue assays were performed to investigate the effects of MBNL1-AS1 and miR-181a-5p on the functions of PCa cells and the expression of PTEN/PI3K/AKT/mTOR signaling by co-transfection with MBNL1-AS1 plasmid and miR-181a-5p mimic. Results indicated that MBNL1-AS1 was conspicuously downregulated while miR-181a-5p upregulating in PCa tissues and cell lines. MBNL1-AS1 overexpression decreased the abilities of cell proliferation, invasion, and migration. Further study revealed that MBNL1-AS1 acted as a sponge for miR-181a-5p and positively regulated PTEN by a sponge effect. Additionally, rescue assays proved that the effect of MBNL1-AS1-upregulation on the proliferation, invasion, and migration of PCa cells was dependent on miR-181a-5p. Furthermore, miR-181a-5p overexpression counteracted the expression of PTEN and proteins in PI3K/AKT/mTOR signaling exerted by MBNL1-AS1-upregulation in PCa cells. This study suggests that MBNL1-AS1 inhibits the progression of PCa via sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR pathway.

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“…Growing evidence suggests that lncRNA acts as a sponge for miRNA in NSCLC progression. For example, the lncRNA muscleblind like splicing regulator 1-AS1 suppresses NSCLC progression by inhibiting cell proliferation, cell cycle progression and metastasis, as well as increasing cell apoptosis by sponging miR-135a-5p ( 21 ). In contrast, lncRNA AWPPH and small nucleolar RNA host gene 4 were found to accelerate cell proliferation, migration, invasion and epithelial-to-mesenchymal transition by sponging miR-204 and miR-98-5p respectively in NSCLC ( 22 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

et al. 2021

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Long non-coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3-AS1 in cancer development has not yet been fully elucidated. The present study focused on non-small cell lung cancer (NSCLC) in order to gain insight into how FOXD3-AS1 drives cancer progression. First, FOXD3-AS1 expression in NSCLC tissue samples was detected using reverse transcription-quantitative (RT-qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3-AS1 and microRNA (miR)-135a-5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3-AS1 in tumor growth. FOXD3-AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3-AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh-NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3-AS1 and miR-135a-5p. Moreover, FOXD3-AS1 silencing led to the upregulation of miR-135a-5p in A549 and H1229 cells compared with sh-NC group. It was also demonstrated that miR-135a-5p could bind to the 3′ untranslated region of cyclin-dependent kinase 6 (CDK6) and negatively modulate its transcription. miR-135a-5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3-AS1 knockdown. Altogether, the present study suggests that FOXD3-AS1 sponges miR-135a-5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.

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Down-regulation of MBNL1-AS1 contributes to tumorigenesis of NSCLC via sponging miR-135a-5p

Cited by 19 publications

References 25 publications

LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer Through MBNL1-AS1/ZFP36/CENPA Axis

LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer Through MBNL1-AS1/ZFP36/CENPA Axis

Muscleblind-like 1 antisense RNA 1 inhibits cell proliferation, invasion, and migration of prostate cancer by sponging miR-181a-5p and regulating PTEN/PI3K/AKT/mTOR signaling

lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

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