Long noncoding RNA SNHG1 promotes TERT expression by sponging miR-18b-5p in breast cancer

Abstract Background Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Results LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis in pan-cancer including breast cancer. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a competing endogenous RNA (ceRNA) to promote TERT expression by sponging miR-18b-5p in breast cancer. miR-18b-5p acted as a tumor repressor in breast cancer. Moreover, the combination of SNHG1 knockdown and TERT inhibitor administration showed a synergistic inhibitory effect on breast cancer growth in vivo. Finally, E2F1 as a transcription factor, binding to SNHG1 promoter and enhanced SNHG1 transcription in breast cancer. Conclusions Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer. Our results also provided a potential treatment for breast cancer when knockdown SNHG1 and TERT inhibitor administration simultaneously.

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Long noncoding RNA SNHG1 promotes TERT expression by sponging miR-18b-5p in breast cancer

10.21203/rs.3.rs-218768/v2 ◽

2021 ◽

Author(s):

yujuan Kang ◽

Lin Wan ◽

Qin Wang ◽

Yanling Yin ◽

Jiena Liu ◽

...

Keyword(s):

Breast Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Malignant Tumors ◽

Positive Role ◽

Nucleolar Rna ◽

Human Malignant Tumors ◽

Tert Expression

Abstract Background: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Results: LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a ceRNA to promote TERT expression by sponging miR-18b-5p. Moreover, miR-18b-5p acted as a tumor repressor in breast cancer. Finally, E2F1, a transcription factor, enhanced SNHG1 transcription.Conclusions: Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer.

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Long Noncoding RNA SNHG1 Promotes TERT Expression by Sponging miR-18b-5p in Breast Cancer

10.21203/rs.3.rs-218768/v1 ◽

2021 ◽

Author(s):

Yujuan Kang ◽

Lin Wan ◽

Qin Wang ◽

Yanling Yin ◽

Jiena Liu ◽

...

Keyword(s):

Breast Cancer ◽

Transcription Factor ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Malignant Tumors ◽

The Cancer Genome Atlas ◽

Luciferase Reporter ◽

Tert Expression

Abstract Background: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Methods: The Cancer Genome Atlas data were used to examine the differential expression of SNHG1 in tumor and normal tissues, as well as the relationship between SNHG1 expression and prognosis. Oncogenic role of SNHG1 in breast cancer was studied both in vitro and in vivo. Animal experiments along with colony counting kit-8, colony formation, wound healing, and Transwell invasion assays were used to verify that SNHG1 was an oncogene in breast cancer. Furthermore, reverse transcription-polymerase chain reaction, western blotting analysis, subcellular RNA fractionation, and dual-luciferase reporter assay were performed to prove the competing endogenous RNA (ceRNA) mechanism of SNHG1, miR-18b-5p, and telomerase reverse transcriptase (TERT). Finally, chromatin immunoprecipitation was performed to confirm that the transcription factor E2F1 could enhance SNHG1 transcription.Results: LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a ceRNA to promote TERT expression by sponging miR-18b-5p. Moreover, miR-18b-5p acted as a tumor repressor in breast cancer. Finally, E2F1, a transcription factor, enhanced SNHG1 transcription.Conclusions: Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer.

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A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Oncogene ◽

10.1038/s41388-020-01638-9 ◽

2021 ◽

Author(s):

Pengpeng Zhu ◽

Fang He ◽

Yixuan Hou ◽

Gang Tu ◽

Qiao Li ◽

...

Keyword(s):

Breast Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Underlying Mechanism ◽

Rapid Expansion ◽

Breast Cancer Patients ◽

Coding Region ◽

Signaling Axis

AbstractThe hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

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Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2014.02.002 ◽

2014 ◽

Vol 141 ◽

pp. 160-170 ◽

Cited By ~ 102

Author(s):

Arunoday Bhan ◽

Imran Hussain ◽

Khairul I. Ansari ◽

Samara A.M. Bobzean ◽

Linda I. Perrotti ◽

...

Keyword(s):

Breast Cancer ◽

Bisphenol A ◽

Long Noncoding Rna ◽

Noncoding Rna

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Long noncoding RNA Linc01296 promotes hepatocellular carcinoma development through regulation of the miR-26a/PTEN axis

Biological Chemistry ◽

10.1515/hsz-2019-0231 ◽

2020 ◽

Vol 401 (3) ◽

pp. 407-416 ◽

Cited By ~ 6

Author(s):

Libin Zhang ◽

Jing Hu ◽

Menghui Hao ◽

Liang Bu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Malignant Tumors ◽

Cell Counting ◽

Tumor Xenograft ◽

Migration And Invasion

AbstractLong noncoding RNA 01296 (Lnc01296) is dysregulated in malignant tumors. However, the detailed effect of Linc01296 on hepatocellular carcinoma (HCC) remains largely unknown. In this study, we identified the biological role of Linc01296 in HCC. The levels of Linc01296 in HCC tissues and a panel of cell lines were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of Linc01296 on HCC progression were explored using a Cell Counting Kit-8 (CCK-8), flow cytometry, migration and Transwell invasion assays. The interactions among Linc01296, miR-26a and PTEN were determined using luciferase, RNA immunoprecipitation (RIP) and Western blot assays. Tumor xenograft models were utilized to confirm the in vivo functional roles of Linc01296 in HCC development. Linc01296 expression was increased in both HCC tissue samples and cell lines. Knockdown of Linc01296 suppressed HCC cell processes, such as proliferation, migration and invasion, and enhanced apoptosis in vitro; these effects were reversed by a miR-26a mimic or PTEN overexpression. Furthermore, knockdown of Linc01296 suppressed HCC growth in vivo. These findings indicated that Linc01296 is involved in HCC progression via regulating miR-26a/PTEN.

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LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

Open Life Sciences ◽

10.1515/biol-2020-0086 ◽

2020 ◽

Vol 15 (1) ◽

pp. 871-883

Author(s):

Jinshan Zhang ◽

Dan Rao ◽

Haibo Ma ◽

Defeng Kong ◽

Xiaoming Xu ◽

...

Keyword(s):

Cell Lines ◽

Noncoding Rna ◽

Xenograft Model ◽

Inhibitory Effect ◽

Cell Counting ◽

Luciferase Reporter ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

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lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15190844870055 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1411-1418 ◽

Cited By ~ 24

Author(s):

Jie Zhang ◽

Xiao-Yan Li ◽

Ping Hu ◽

Yuan-Sheng Ding

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Noncoding Rna ◽

Cancer Metastasis ◽

Cellular Proliferation ◽

Inhibitory Effect ◽

Migration And Invasion ◽

Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

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Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA

eLife ◽

10.7554/elife.67250 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ki-Sun Park ◽

Beenish Rahat ◽

Hyung Chul Lee ◽

Zu-Xi Yu ◽

Jacob Noeker ◽

...

Keyword(s):

Endothelial Cells ◽

Ventricular Function ◽

Mouse Models ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Relative Importance ◽

Maternal Loss ◽

Loss Of Imprinting

Maternal loss of imprinting (LOI) at the H19/IGF2 locus results in biallelic IGF2 and reduced H19 expression and is associated with Beckwith-Wiedemann syndrome (BWS). We use mouse models for LOI to understand the relative importance of Igf2 and H19 mis-expression in BWS phenotypes. Here we focus on cardiovascular phenotypes and show that neonatal cardiomegaly is exclusively dependent on increased Igf2. Circulating IGF2 binds cardiomyocyte receptors to hyperactivate mTOR signaling, resulting in cellular hyperplasia and hypertrophy. These Igf2-dependent phenotypes are transient: cardiac size returns to normal once Igf2 expression is suppressed postnatally. However, reduced H19 expression is sufficient to cause progressive heart pathologies including fibrosis and reduced ventricular function. In the heart, H19 expression is primarily in endothelial cells (ECs) and regulates EC differentiation both, in vivo and in vitro. Finally, we establish novel mouse models to show that cardiac phenotypes depend on H19 lncRNA interactions with Mirlet7 microRNAs.

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Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats

Pharmaceutics ◽

10.3390/pharmaceutics12050397 ◽

2020 ◽

Vol 12 (5) ◽

pp. 397

Author(s):

Yoo-Kyung Song ◽

Jin-Ha Yoon ◽

Jong Kyu Woo ◽

Ju-Hee Kang ◽

Kyeong-Ryoon Lee ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Resistance Protein ◽

Fold Increase ◽

Inhibitory Effect ◽

Dependent Manner ◽

Cancer Resistance ◽

Concentration Dependent Manner ◽

Resistance Protein

The potential inhibitory effect of quercetin, a major plant flavonol, on breast cancer resistance protein (BCRP) activity was investigated in this study. The presence of quercetin significantly increased the cellular accumulation and associated cytotoxicity of the BCRP substrate mitoxantrone in human cervical cancer cells (HeLa cells) in a concentration-dependent manner. The transcellular efflux of prazosin, a stereotypical BCRP substrate, was also significantly reduced in the presence of quercetin in a bidirectional transport assay using human BCRP-overexpressing cells; further kinetic analysis revealed IC50 and Ki values of 4.22 and 3.91 μM, respectively. Moreover, pretreatment with 10 mg/kg quercetin in rats led to a 1.8-fold and 1.5-fold increase in the AUC8h (i.e., 44.5 ± 11.8 min∙μg/mL vs. 25.7 ± 9.98 min∙μg/mL, p < 0.05) and Cmax (i.e., 179 ± 23.0 ng/mL vs. 122 ± 23.2 ng/mL, p < 0.05) of orally administered sulfasalazine, respectively. Collectively, these results provide evidence that quercetin acts as an in vivo as well as in vitro inhibitor of BCRP. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, issuing a caution regarding its food–drug interactions should be considered.

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