Exosomal Long Non-coding RNA HOTTIP Increases Resistance of Colorectal Cancer Cells to Mitomycin via Impairing MiR-214-Mediated Degradation of KPNA3

It has been reported that long non-coding RNA HOXA distal transcript antisense RNA (lncRNA HOTTIP) functions as a tumor promoter in colorectal cancer (CRC). Hence, we paid attention to exploring whether exosomes could carry lncRNA HOTTIP to affect the mitomycin resistance in CRC and to identify the underlying mechanisms. High expression of HOTTIP was detected in mitomycin-resistant CRC cells. Inhibition of HOTTIP reduced the mitomycin resistance. In the co-culture system of mitomycin-resistant cells or their derived exosomes with CRC cells, the HOTTIP was found to be transferred into the parental cells via extracellular vesicles (EVs) secreted from mitomycin-resistant cells and to contribute to the mitomycin resistance. Based on the bioinformatics databases, possible interaction network of HOTTIP, microRNA-214 (miR-214) and Karyopherin subunit alpha 3 (KPNA3) in CRC was predicted, which was further analyzed by dual-luciferase reporter, RNA binding protein immunoprecipitation and RNA pull-down assays. As HOTTIP down-regulated miR-214 to elevate the KPNA3 expression, HOTTIP enhanced the mitomycin resistance through impairing miR-214-dependent inhibition of KPNA3. Finally, HOTTIP was suggested as an independent factor predicting mitomycin response in patients with CRC. Those data together confirmed the promotive effects of EV-carried HOTTIP on the mitomycin resistance, while targeting HOTTIP might be a promising strategy overcoming drug resistance in CRC.

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Downregulation of long non-coding RNA ZXF1 restricts cell survival by targeting miR-634-GRB2 in lung adenocarcinoma

Acta Biochimica Polonica ◽

10.18388/abp.2020_2875 ◽

2020 ◽

Author(s):

Xubin Ren ◽

Nie Xu ◽

Yunting Zhang ◽

Tao Wang

Keyword(s):

Lung Adenocarcinoma ◽

Luciferase Reporter ◽

Normal Tissues ◽

Non Coding Rna ◽

Enhanced Expression ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms ◽

First Time ◽

Long Non Coding Rna

Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play important regulatory roles in mediating initiation and progression of lung adenocarcinoma (LA), which is one of the most lethal in humans. A previous study reported that lncRNAZXF1 was dysregulated in LA and enhanced expression of ZXF1 promoted the invasion and metastasis in LA. However, the effect of ZXF1 on LA progression and its underlying mechanisms were not thoroughly investigated. In our in vitro experiments, qRT-PCR revealed that the expression level of ZXF1 in LA tissues and tumor cells were significantly higher than that in adjacent normal tissues and normal cells. Furthermore, bioinformatics analysis, luciferase reporter assay, western blot and RNA immunoprecipitation (RIP) assay showed that ZXF1 could directly interact with miR-634, which targets GRB2. Therefore, we propose that ZXF1 could function as an oncogene partly by sponging miR-634 and therefore regulating GRB2 expression in LA. Overall, this study demonstrated, for the first time, that the lncRNA ZXF1/miR-634/GRB2 axis plays crucial roles in modulating LA progression. Moreover, lncRNA ZXF1 might potentially improve LA prognosis and serve as a therapeutic target for the treatment of LA.

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LncRNA H19 Upregulation Participates in the Response of Glioma Cells to Radiation

BioMed Research International ◽

10.1155/2021/1728352 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yanbei Kuang ◽

Zhitong Bing ◽

Xiaodong Jin ◽

Qiang Li

Keyword(s):

Molecular Level ◽

Glioma Cells ◽

Luciferase Reporter ◽

X Rays ◽

Cycle Arrest ◽

Non Coding Rna ◽

Cell Processes ◽

Underlying Mechanisms ◽

Long Non Coding Rna ◽

Radiotherapy Failure

Previous studies have indicated that radiation resistance of glioma is one of the leading causes of radiotherapy failure. Mounting evidence suggests that long non-coding RNA (lncRNA) plays an important role in regulating radiosensitivity of cancer cells via implicating in various cell processes. However, the underlying mechanisms remain unclear and need further study, especially at the molecular level. We found that the expression level of lncRNA H19 was elevated by radiation, and then, the modulation of H19 affected the resistant of glioma cells to X-rays. Dual-luciferase reporter analyses showed that H19 was transcriptionally activated by CREB1 in glioma cells after irradiation. In addition, both flow cytometry and 5-ethynyl-2 ′ -deoxyuridine (EdU) assay suggested that H19 was involved in the cell cycle arrest, apoptosis, and DNA synthesis to modulate the radiation response of glioma cells and influenced their radioresistance. Therefore, H19 might play a crucial role in enhancing the radioresistance of glioma.

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Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells

Cancer Cell International ◽

10.1186/s12935-020-01549-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Changru Fan ◽

Qiulan Yuan ◽

Guifeng Liu ◽

Yuliang Zhang ◽

Maojun Yan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Malignant Tumors ◽

Cell Counting ◽

Luciferase Reporter ◽

Western Blot Assay ◽

Resistance Response ◽

Non Coding Rna ◽

Colorectal Cancer Cells ◽

Long Non Coding Rna

Abstract Background Colorectal cancer (CRC) is one of the most general malignant tumors. Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC. However, the effect of MALAT1 in drug-resistance needed to be further illustrated. Methods Levels of MALAT1, microRNA (miR)-324-3p, and a disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit 8 (CCK-8) was used to assess the half maximal inhibitory concentration (IC50) of oxaliplatin (Ox). Meanwhile, cell proliferation, migration and apoptosis were detected by CCK-8, transwell assay, and flow cytometry, respectively. The interaction between miR-324-3p and MALAT1 or ADAM17 was clarified by dual-luciferase reporter assay. Also, the effect of MALAT1 on tumor growth was detected in xenograft tumor mice treated with Ox. Results Significant up regulation of MALAT1 and ADAM17, and decrease of miR-324-3p were observed in Ox-resistant CRC tissues and cells. MALAT1 deficiency enhanced the sensitivity of Ox-resistant CRC cells response to Ox, while miR-324-3p repression or ADAM17 acceleration could overturn this effect. Moreover, MALAT1 silencing repressed tumor growth in Ox-treated nude mice. Mechanically, MALAT1 exerted promotion effect on the resistance response to Ox via miR-324-3p/ADAM17 axis in Ox-resistant CRC cells. Conclusion MALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.

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The long non-coding RNA SNHG5 regulates gefitinib resistance in lung adenocarcinoma cells by targetting miR-377/CASP1 axis

Bioscience Reports ◽

10.1042/bsr20180400 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 11

Author(s):

ZheXing Wang ◽

LiMing Pan ◽

HaiXiang Yu ◽

Yue Wang

Keyword(s):

Lung Adenocarcinoma ◽

Luciferase Reporter ◽

Functional Assay ◽

Downstream Target ◽

Non Coding Rna ◽

Gefitinib Treatment ◽

Underlying Mechanisms ◽

Gefitinib Resistance ◽

Long Non Coding Rna

Gefitinib resistance is one of the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down-regulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that SNHG5 exerted its function through interaction with miR-377, which was further confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5 suppressed the expression of miR-377, while the knockdown of SNHG5 increased the miR-377 expression. MiR-377 expression was significantly up-regulated in LAD specimens with acquired gefitinib resistance and was negatively correlated with SNHG5 expression. In addition, CASP1 was predicted as a downstream target of miR-377. Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells and knockdown of miR-377 increased the CASP1 expression in PC9GR cells. In vitro functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance. Overall, the present study demonstrated, for the first time, that the SNHG5/miR-377/CASP1 axis functions as an important role in LAD cells gefitinib resistance and potentially contributes to the improvement of LAD diagnosis and therapy.

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Long Non-coding RNA MAFG-AS1 Promotes Cell Proliferation, Migration, and EMT by miR-3196/STRN4 in Drug-Resistant Cells of Liver Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.688603 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tianming Chen ◽

Bin Huang ◽

Yaozhen Pan

Keyword(s):

Colorectal Cancer ◽

Drug Resistant ◽

Non Coding Rna ◽

Different Types ◽

Non Coding Rnas ◽

Novel Target ◽

And Migration ◽

Long Non Coding Rna ◽

Resistant Cells

Long non-coding RNAs (lncRNAs) have been shown to participate in the development and progression of several different types of cancer. Past studies indicated that lncRNA MAFG-antisense 1 (AS1) promotes colorectal cancer. However, the role of MAFG-AS1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study is to examine the effect of lncRNA MAFG-AS1 on drug resistance HCC. The results indicated that MAFG-AS1 is upregulated in drug-resistant cells. Further, MAFG-AS1 promotes growth and migration of HCC by upregulating STRN4 through absorbing miR-3196. Thus, LncRNA MAFA-AS1 may become a novel target to treat HCC patients.

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LncRNA ZEB1-AS1 regulates colorectal cancer cells by miR-205/YAP1 axis

Open Medicine ◽

10.1515/med-2020-0026 ◽

2020 ◽

Vol 15 (1) ◽

pp. 175-184 ◽

Cited By ~ 2

Author(s):

Zhong Jin ◽

Bing Chen

Keyword(s):

Colorectal Cancer ◽

Cell Viability ◽

Luciferase Reporter ◽

Non Coding Rna ◽

Colorectal Cancer Cells ◽

Non Coding Rnas ◽

Induced Apoptosis ◽

The Relationship ◽

Long Non Coding Rna ◽

Inhibit Cell Proliferation

AbstractBackgroundRecent studies demonstrated that long non-coding RNAs (lncRNAs) were involved in many biological processes. Dysregulated lncRNAs are related to many cancers, including colorectal cancer (CRC). However, the molecular mechanism of lncRNA ZEB1-AS1 in CRC is not clear.MethodsLncRNA ZEB1-AS1, miR-205, and YAP1 expression were measured by quantitative reverse transcriptase PCR (QRT-PCR). YAP1 protein expression was measured by western blotting. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was used to confirm the relationship between ZEB1-AS1, miR-205, and YAP1.ResultsLncRNA ZEB1-AS1 and YAP1 was upregulated in CRC tissues. The expression of YAP1 was positively correlated with ZEB1-AS1. Knockdown of ZEB1-AS1 inhibited cell viability and induced apoptosis in CRC cell line SW480 and HCT116 which could be reversed by overexpression of YAP1. ZEB1-AS1 targeted and regulated miR-205 which could directly bind to YAP1. Meanwhile, ZEB1-AS1 regulated the expression of YAP1 via modulating miR-205.ConclusionLong non-coding RNA ZEB1-AS1 silencing could inhibit cell proliferation and induce apoptosis of colorectal cancer via regulating miR-205 and YAP1.

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MAGI2-AS3 Modulates Proliferation, Apoptosis and Glycolysis in Acute Lymphoblastic Leukemia via miR-452-5p/FOXN3 Axis

10.21203/rs.3.rs-757502/v1 ◽

2021 ◽

Author(s):

Xiao-Guang Chen ◽

Bing-Hua Dou ◽

Jin-Dou An ◽

Song Feng ◽

Na Liu ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Lactate Production ◽

Xenograft Model ◽

Luciferase Reporter ◽

Protein Levels ◽

Non Coding Rna ◽

Underlying Mechanisms ◽

Long Non Coding Rna

Abstract Background: Long non-coding RNA MAGI2 antisense RNA 3 (MAGI2-AS3) has been identified as a tumor suppressor in various cancers. Acute lymphoblastic leukemia (ALL) is a prevalent kind of leukemia among children. In this study, we aimed at evaluate the role of MAGI2-AS3 in ALL and its underlying mechanisms.Methods: qPCR was adopted to determine MAGI2-AS3, miR-452-5p, and FOXN3 expression. The malignant properties of ALL cells were assessed by CCK8 assay and flow cytometry analysis. The glucose uptake, lactate production, and ATP level were measured to evaluate glycolysis. Western blotting was performed to detect PCNA, Bcl-2, Bax, and HK2 protein levels. The interaction between MAGI2-AS3/FOXN3 and miR-452-5p was validated by luciferase reporter assay. The in vivo growth of ALL cells was determined in xenograft model.Results: MAGI2-AS3 was strikingly down-regulated in ALL samples and cells. Overexpression of MAGI2-AS3 restrained growth, glycolysis and triggered apoptosis of ALL cells. Mechanistically, MAGI2-AS3 could sponge miR-452-5p to up-regulate FOXN3. Silencing of FOXN3 abolished the anti-tumor effect of MAGI2-AS3. Finally, MAGI2-AS3 suppressed the in vivo growth of ALL cells via modulating miR-452-5p/FOXN3 axis. Conclusions: Our findings demonstrate that MAGI2-AS3 delays the progression of ALL by regulating miR-452-5p/FOXN3 signaling pathway.

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Long Non-Coding RNA CBR3-AS1 Promotes Stem-Like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p

10.21203/rs.3.rs-58142/v1 ◽

2020 ◽

Author(s):

Liangbao Xie ◽

Guangfei Cui ◽

Tao Li

Keyword(s):

Colorectal Cancer ◽

Direct Interaction ◽

Luciferase Reporter ◽

Expression Levels ◽

Mammosphere Formation ◽

Normal Tissues ◽

Non Coding Rna ◽

Rna Immunoprecipitation ◽

Long Non Coding Rna

Abstract Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.

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Long non-coding RNA SNHG16 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer via sponging miR-200a-3p

Bioscience Reports ◽

10.1042/bsr20182498 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 4

Author(s):

Yanling Li ◽

Ying Lu ◽

Yanglong Chen

Keyword(s):

Colorectal Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Loss Of Function ◽

Non Coding Rna ◽

Promote Tumor Growth ◽

Cell Growth And Proliferation ◽

Long Non Coding Rna

Abstract Previous study has explored that SNHG16, a long non-coding RNA (lncRNA), mediated cell growth and proliferation. Yet, the role of SNHG16 in human colorectal cancer (CRC) still remains to be explored. Therefore, we conducted the present study to explore the functions of SNHG16 in CRC. In the present study, SNHG16 was significantly up-regulated in CRC tissues and cell lines. Gain- and loss-of-function of SNHG16 further presented that SNHG16 promoted the progression of CRC cells, including proliferation, migration, and invasion. Further, in vivo study also revealed that overexpression of SNHG16 could promote tumor growth. Bioinformatics analysis and luciferase reporter assay showed that SNHG16 was a direct target of miR-200a-3p. MiR-200a-3p was inversely correlated with SNHG16 expression in CRC tissues. In brief, the above results elucidate the important role of SNHG16 in CRC tumorigenesis, suggesting that SNHG16 might be quite vital for the diagnosis and development of CRC.

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Long Non-Coding RNA LINC01569 Promotes Proliferation and Metastasis in Colorectal Cancer by miR-381-3p/RAP2A Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.727698 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guang-yao Ye ◽

Zi-zhen Zhang ◽

Chun-chao Zhu ◽

Zhi-jie Cong ◽

Zhe Cui ◽

...

Keyword(s):

Colorectal Cancer ◽

Expression Profiles ◽

Subcellular Fractionation ◽

Luciferase Reporter ◽

Regulatory Function ◽

Loss Of Function ◽

Tumor Onset ◽

Non Coding Rna ◽

Proliferation And Metastasis ◽

Long Non Coding Rna

BackgroundLong non-coding RNAs (lncRNAs) display regulatory function flexibly in tumor onset and developments. Our study aimed to delve into the roles of lncRNA LINC01569 (LINC01569) in colorectal cancer (CRC) progression to study the potential mechanisms.MethodsThe genetic expression profiles of miR-381-3p and LINC01569 were measured by RT-PCR. The subcellular localization of LINC01569 in CRC cells was identified using subcellular fractionation location. Loss-of-function assays were performed to explore the potential effects of LINC01569 on CRC progression. Dual-luciferase reporter analysis was employed to verify the binding connections among LINC01569, miR-381-3p, and RAP2A.ResultsLINC01569 expression was distinctly increased in CRC. Curiously, if LINC01569 is removed, CRC cells will not migrate, proliferate, and invade remarkably. Molecular mechanism exploration uncovered that LINC01569 acted as a ceRNA competing with RAP2A to bind with miR-381-3p. Furthermore, rescue experiments corroborated the fact that miR-381-3p suppression reversed the inhibitory actions of LINC01569 knockdown on the expression of RAP2A and CRC progression.ConclusionOverall, our findings indicate that LINC01569 plays a key role in CRC development by means of aiming at the miR-381-3p/RAP2A axis and can be equivalent to an underlying medicinal target to save CRC patients.

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