scholarly journals Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xueshan Zhao ◽  
Xiaodong Jin ◽  
Qiuning Zhang ◽  
Ruifeng Liu ◽  
Hongtao Luo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Therapeutic Target ◽  
Ion Irradiation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Antitumor Effects ◽  
Carbon Ion ◽  
X Ray

Abstract Background The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. Methods The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). Results Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. Conclusion Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

scholarly journals Silencing of lncRNA H19 Enhances the Sensitivity to X-rays and Carbon-Ions Through the miR-130a-3p /WNK3 Signal Axis in Non-Small-Cell Lung Cancer Cells

2021 ◽  
Author(s):  
Xueshan Zhao ◽  
Xiaodong Jin ◽  
Qiuning Zhang ◽  
Ruifeng Liu ◽  
Hongtao Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Ion Irradiation ◽  
Expression Profiles ◽  
Small Cell ◽  
X Rays ◽  
Small Cell Lung ◽  
Carbon Ion

Abstract Background: LncRNA H19 was believed to act as an oncogene in various types of tumors and was considered to be a therapeutic target and diagnosis marker. However, the role of lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells was unknown. However, the effects of lncRNA H19 on radiosensitivity of NSCLC were not clear. Methods: The expression profiles of lncRNAs were explored via transcriptome sequencing in NSCLC. The CCK-8, EDU, and clonogenicity survival assay were conducted to explore the proliferation and radiosensitivity in NSCLC cells. Results: Expression patterns of lncRNAs revealed that compared with A549 cells, lncRNA H19 was upregulated in radioresistant NSCLC(A549-R11) cells. Knockdown experiments revealed that lncRNA H19 enhanced the radiation sensitivity of both A549 and H460 cancer cell lines to X-rays and carbon ion irradiation. Mechanistically, lncRNA H19 upregulated With-No-Lysine Kinase 3 (WNK3) expression via serving as a sponge of miR-130a-3p and promoted the resistance of NSCLC cells to both X-rays and carbon ion irradiation. Conclusion: Knockdown of lncRNA H19 promoted the radiation sensitivity of NSCLC cells to X-rays and carbon ion irradiation. Hence, lncRNA H19 might function as a potential therapeutic target which enhance the anti-tumor effects of radiotherapy in NSCLC.

scholarly journals Genetic Effects of X-Ray and Carbon Ion Irradiation in Head and Neck Carcinoma Cell Lines

2007 ◽  
Vol 48 (4) ◽  
pp. 177-185 ◽  
Author(s):  
Nobuharu Yamamoto ◽  
Chihaya Ikeda ◽  
Takashi Yakushiji ◽  
Takeshi Nomura ◽  
Akira Katakura ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Ion Irradiation ◽  
Head And Neck Carcinoma ◽  
Genetic Effects ◽  
Carbon Ion ◽  
X Ray ◽  
Carcinoma Cell Lines ◽  
Neck Carcinoma

scholarly journals Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells

2017 ◽  
Vol 58 (6) ◽  
pp. 765-771 ◽  
Author(s):  
Seong-Joon Park ◽  
Kyu Heo ◽  
Chulwon Choi ◽  
Kwangmo Yang ◽  
Akiko Adachi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Ion Irradiation ◽  
Ion Beam ◽  
Melanoma Cells ◽  
Micro Rna ◽  
Carbon Ion ◽  
X Ray ◽  
Melanoma Cell Lines

Abstract The Lin28/let-7 axis plays an important role in tumor initiation and developmental processes. Lin28B is upregulated in a variety of cancers, and its overexpression enhances cancer cell proliferation and radioresistance through the suppression of let-7 micro RNA expression. In this study, we investigated the role of the Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of cancer stem cell (CSC) populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Consistent with these results, Lin28B overexpression reduced the numbers of γH2A.X foci after X-ray irradiation, whereas carbon ion irradiation had no such effect. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.

scholarly journals Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing

2018 ◽  
Vol 51 (6) ◽  
pp. 2509-2522 ◽  
Author(s):  
Shousen Hu ◽  
Yongliang Yuan ◽  
Zhizhen Song ◽  
Dan Yan ◽  
Xiangzhen Kong
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Profiles ◽  
Small Cell ◽  
Nsclc Cell ◽  
Drug Resistant ◽  
Small Cell Lung

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.

scholarly journals Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Hartmann ◽  
Philipp Schröter ◽  
Wolfram Osen ◽  
Daniel Baumann ◽  
Rienk Offringa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Ion Irradiation ◽  
Dose Range ◽  
Cancer Cell Line ◽  
Surface Expression ◽  
Photon Radiation ◽  
Immunomodulatory Effects ◽  
Carbon Ion ◽  
Dose Dependent

AbstractWhile for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-Db and H2-Kb was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.

scholarly journals Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Yunpeng Liu ◽  
Xingyu Lin ◽  
Shiyao Zhou ◽  
Peng Zhang ◽  
Guoguang Shao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung

Abstract Background: The HOXA cluster antisense RNA 2 (HOXA-AS2) has recently been discovered to be involved in carcinogenesis in multiple cancers. However, the role and underlying mechanism of HOXA-AS2 in non-small cell lung cancer (NSCLC) yet need to be unraveled. Methods: HOXA-AS2 expression in NSCLC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). Furthermore, the effects of HOXA-AS2 on NSCLC cell proliferation, apoptosis, migration, and invasion were assessed by MTS, flow cytometry, wound healing and transwell invasion assays, respectively. Starbase2.0 predicted and luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the association of HOXA-AS2 and miR-520a-3p in NSCLC cells. Results: Our results revealed that HOXA-AS2 in NSCLC tissues were up-regulated and cell lines, and were associated with poor prognosis and overall survival. Further functional assays demonstrated that HOXA-AS2 knockdown significantly inhibited NSCLC cell proliferation, induced cell apoptosis and suppressed migration and invasion. Starbase2.0 predicted that HOXA-AS2 sponge miR-520a-3p at 3′-UTR, which was confirmed using luciferase reporter and RIP assays. miR-520a-3p expression was inversely correlated with HOXA-AS2 expression in NSCLC tissues. In addition, miR-520a-3p inhibitor attenuated the inhibitory effect of HOXD-AS2-depletion on cell proliferation, migration and invasion of NSCLC cells. Moreover, HOXA-AS2 could regulate HOXD8 and MAP3K2 expression, two known targets of miR-520a-3p in NSCLC. Conclusion: These findings implied that HOXA-AS2 promoted NSCLC progression by regulating miR-520a-3p, suggesting that HOXA-AS2 could serve as a therapeutic target for NSCLC.

Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib

2012 ◽  
Vol 66 (5) ◽  
pp. 384-389 ◽  
Author(s):  
Ruitong Xu ◽  
Hua Shen ◽  
Renhua Guo ◽  
Jing Sun ◽  
Wen Gao ◽  
...  
Keyword(s):  
Cell Lines ◽  
Combine Therapy ◽  
Acquired Resistance ◽  
Nsclc Cell ◽  
Antitumor Effects

scholarly journals Systematic analysis of mRNA expression profiles in NSCLC cell lines to screen metastasis-related genes

2016 ◽  
Vol 14 (6) ◽  
pp. 5093-5103 ◽  
Author(s):  
Ying Liu ◽  
Lei Liu ◽  
Tao Yu ◽  
He-Chun Lin ◽  
Dandan Chu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Expression Profiles ◽  
Nsclc Cell ◽  
Systematic Analysis

Cytotoxicity Assessment of Quassinoids Neosergeolide and Isobrucein B toward Hematopoietic and Solid Malignancies Identifies STAT3 Activation To Be Predictive of Antitumor Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1394-1394
Author(s):  
Mitsuteru Hiwatari ◽  
Jingqiu Dai ◽  
Wei Liu ◽  
Yu-Dong Zhou ◽  
Dale G. Nagle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Strong Support ◽  
Luciferase Reporter ◽  
Control Group ◽  
Antitumor Effects ◽  
Protein Levels ◽  
Ic50 Values

Abstract Quassinoids are natural product compounds known to possess tumor cytotoxicity and antimalarial activity. Neosergiolide and isobrucein B are two quassinoids previously isolated from roots and stems of Picrolemma sprucei. In screening studies to identify inhibitors that target STAT3, we discovered neosergeolide and isobrucein B as active compounds. Approximately 5000 plant-derived extracts were screened using a cell line that stably expresses a STAT3-dependent luciferase reporter and NPM-ALK, which constitutively induces STAT3 transcriptional activity. Of 25 total hits, a P. sprucei extract was potent and selective for STAT3 inhibition, and bioassay-guided isolation identified neosergeolide and isobrucein B as the inhibitory compounds. Western blot analysis confirmed that neosergeolide and isobrucein B not only inhibit the tyrosine phosphorylation and activation of STAT3 but also decrease total STAT3 protein levels via a mechanism due in part to enhanced proteasome-mediated degradation. Small-molecule proteasome inhibitors such as MG132 and ALLN reversed the ability of the two quassinoids to decrease STAT3 protein levels; furthermore, simultaneous incubation of various hematopoietic malignancy cell lines with either neosergeolide or isobrucein B and MG132 or ALLN antagonized the cytotoxic activity of the quassinoids. Assessment of neosergiolide and isobrucein B antitumor effects using an XTT assay revealed both compounds to possess potent cytotoxic activity across a broad spectrum of hematopoietic malignancies, with T-leukemias/lymphomas being especially responsive. For example, mycosis fungoides (MF)- and Sezary syndrome (SS)-derived cell lines, as well as non-MF/SS cutaneous T-cell lymphoma (CTCL) lines, were potently inhibited by both quassinoids (neosergiolide IC50 values: MAC-1, 11.6 nM; MAC-2A, 6.9 nM; Hut-78, 6.6 nM; HH, 4.3 nM; MJ, 7.0 nM; isobrucein B IC50 values: MAC-1, 31.9 nM; MAC-2A, 72.3 nM; Hut-78, 23.5 nM; HH; 20.3 nM; MJ, 13.5 nM). Non-hematopoietic cell lines representing various solid tumors also exhibited potent cytotoxic responses to the quassinoids (e.g., gastric carcinoma line AGS [neosergiolide IC50: 16.9 nM; isobrucein B IC50: 114.9 nM]). With rare exceptions, the cytotoxicity of the quassinoids against a specific tumor cell line correlated with STAT3 activation status; for example, breast cancer line MCF7 with inactive STAT3 was resistant to both quassinoids even at the maximum concentration tested (6.25 μM), whereas breast cancer lines MDA-MB-468 and MDA-MB-435s with activated STAT3 were inhibited by both compounds at low concentrations (neosergiolide IC50: MDA-MB-435s, 31.3 nM; MDA-MB-468, 29.9 nM; isobrucein B IC50: MDA-MB-435s, 209.3 nM; MDA-MB-468, 356.8 nM). The in vitro antitumor activity of the two quassinoids could also be demonstrated in vivo. For example, isobrucein B (1.0 mg/kg IP once q 3d x 5 doses) could be safely administered and potently inhibited the growth in SCID mice of the CD30+ primary CTCL MAC-1 cell line; mice at treatment day 16 showed average subcutaneous tumor volumes of 3839 ± 863 (s.e.) mm3 in the vehicle-control group and 913 ± 349 (s.e.) mm3 in the isobrucein B group (P=0.008, t-test). These results provide strong support for STAT3 targeting in antitumor drug discovery and suggest that quassinoids may have utility in such an approach.

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