Knockdown of c-Myc activates Fas-mediated apoptosis and sensitizes A549 cells to radiation

Zhang, Jing; Zhou, Ling; Nan, Zhaodi; Yuan, Qing; Wen, Jie; Xu, Maolei; Li, Youjie; Li, Baosheng; Wang, Pingyu; Liu, Changmin; Ma, Ying; Chen, Shaoshui; Xie, Songqiang

doi:10.3892/or.2017.5897

Cited by 25 publications

(16 citation statements)

References 39 publications

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“…Interestingly, SLFN12 overexpression increased the number of apoptotic cells in all of the three tested LUAD cell models. Although c-myc knockdown reported to induce apoptosis in lung cancer cells [ 36 ], it still needs to be determined if SLFN12 induces apoptosis through c-myc pathway or another independent pathway.…”

Section: Discussionmentioning

confidence: 99%

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma

Al-Marsoummi

Pacella

Dockter

et al. 2020

Cancers

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Schlafen 12 (SLFN12) is an intermediate human Schlafen that induces differentiation in enterocytes, prostate, and breast cancer. We hypothesized that SLFN12 influences lung cancer biology. We investigated survival differences in high versus low SLFN12-expressing tumors in two databases. We then adenovirally overexpressed SLFN12 (AdSLFN12) in HCC827, H23, and H1975 cells to model lung adenocarcinoma (LUAD), and in H2170 and HTB-182 cells representing lung squamous cell carcinoma (LUSC). We analyzed proliferation using a colorimetric assay, mRNA expression by RT-qPCR, and protein by Western blot. To further explore the functional relevance of SLFN12, we correlated SLFN12 with seventeen functional oncogenic gene signatures in human tumors. Low tumoral SLFN12 expression predicted worse survival in LUAD patients, but not in LUSC. AdSLFN12 modulated expression of SCGB1A1, SFTPC, HOPX, CK-5, CDH1, and P63 in a complex fashion in these cells. AdSLFN12 reduced proliferation in all LUAD cell lines, but not in LUSC cells. SLFN12 expression inversely correlated with expression of a myc-associated gene signature in LUAD, but not LUSC tumors. SLFN12 overexpression reduced c-myc protein in LUAD cell lines but not in LUSC, by inhibiting c-myc translation. Our results suggest SLFN12 improves prognosis in LUAD in part via a c-myc-dependent slowing of proliferation.

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Section: Discussionmentioning

confidence: 99%

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma

Al-Marsoummi

Pacella

Dockter

et al. 2020

Cancers

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“…MAPK signaling has been demonstrated to be related to the cellular senescence process [26,27]. Fas induction causes apoptosis by activating caspase-8 [28]. The NF-κB signaling pathway is a potential inducer for chondrocyte apoptosis [29,30].…”

Section: Discussionmentioning

confidence: 99%

Loganin Attenuates Osteoarthritis in Rats by Inhibiting IL-1β-Induced Catabolism and Apoptosis in Chondrocytes Via Regulation of Phosphatidylinositol 3-Kinases (PI3K)/Akt

Yang

Zhao

et al. 2019

Med Sci Monit

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Background Chondrocyte apoptosis and catabolism are 2 major factors that contribute to the progression of osteoarthritis (OA). Loganin, an iridoid glycoside present in several herbs, including Flos lonicerae , Cornus mas L , and Strychnos nux vomica, is a valuable medication with anti-inflammatory and anti-apoptotic effects . Our study examines these effects and explores the potential benefits of loganin in the OA treatment. Material/Methods To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1β and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor). The apoptotic level, catabolic factors (MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5), extracellular matrix (ECM) degradation, and activation of the PI3K/Akt pathway were evaluated using western blotting, PCR, and an immunofluorescent assay. The degenerative condition of the cartilage was evaluated using the Safranin O assay in vivo . The expression of cleaved-caspase-3 (C-caspase-3) was measured using immunochemistry. Results The data suggested that loganin suppressed the apoptotic level, reduced the release of catabolic enzymes, and decreased the ECM degradation of IL-1β-induced chondrocytes. However, suppressing PI3K/Akt signaling using LY294002 alleviated the therapeutic effects of loganin in chondrocytes. Our in vivo experiment showed that loganin partially attenuated cartilage degradation while inhibiting the apoptotic level. Conclusions This work revealed that loganin treatment attenuated IL-1β-treated apoptosis and ECM catabolism in rat chondrocytes via regulation of the PI3K/Akt signaling, revealing that loganin is a potentially useful treatment for OA.

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“…To date, as we know, c-Myc plays an important role in the mediation of chemoradiation resistance and increase in c-Myc expression promoted the activity of poly(ADP-ribose) polymerase (PARP)-dependent DNA repair pathways and contributed to chemoresistance 41. c-Myc also induced expression of CHK1 and CHK2 to subsequently activate the DNA-damage-checkpoint response in radioresistance of nasopharyngeal carcinoma cells,42 whereas knockdown of c-Myc expression induced Fas-mediated apoptosis to sensitize lung cancer cells to radiation43 Thus, in any events, targeting of the LINC00958-c-Myc network could induce sensitivity of HNSCC cells to cisplatin and ionizing radiation.…”

Section: Discussionmentioning

confidence: 99%

<p>LINC00958-MYC positive feedback loop modulates resistance of head and neck squamous cell carcinoma cells to chemo- and radiotherapy in vitro</p>

Huang¹,

Zhan²,

Li³

et al. 2019

OTT

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Background Aberrant long non-coding RNA (lncRNA) expression contributes cancer development and resistance to therapy. This study first assessed expression of lncRNA LINC00958 in a variety of human cancers using GEPIA database data and then associated it with prognosis of head and neck squamous cell carcinoma (HNSCC) and investigated LINC00958 interaction with c-Myc and the c-Myc-related gene interplay in HNSCC cells. Materials and methods A cohort of 48 HNSCC vs normal tissues was collected for qRT-PCR analysis of LINC00958 and c-Myc expression and statistical analyses. HNSCC cell lines were subjected to transfection with LINC00958 and c-Myc siRNAs or cDNA and their negative control siRNA or empty vector for qRT-PCR, Western blot, cell viability, colony formation, luciferase reporter, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Results The data showed that LINC00958 expression was upregulated in HNSCC tissues and cell lines, upregulation of which was associated with poor tumor differentiation, advanced tumor stage, and shorter overall survival of patients. In vitro, LINC00958 expression induced HNSCC cell viability and colony formation, whereas knockdown of LINC00958 expression enhanced HNSCC cell sensitivity to ionizing radiation and cisplatin treatment. Mechanistically, LINC00958 is a direct target of c-Myc and can enhance the transcriptional activity of c-Myc, thus to form a positive feedback gene network in HNSCC cells, and in turn to modulate HNSCC cell resistance to chemo- and radiotherapy. Conclusion This study demonstrated the LINC00958 interplay with c-Myc as a feedback loop facilitated HNSCC development and resistance to chemo- and radiotherapy. Targeting of such a network could be further evaluated as a novel therapeutic strategy for HNSCC patients.

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Knockdown of c-Myc activates Fas-mediated apoptosis and sensitizes A549 cells to radiation

Cited by 25 publications

References 39 publications

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma

Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma

Loganin Attenuates Osteoarthritis in Rats by Inhibiting IL-1β-Induced Catabolism and Apoptosis in Chondrocytes Via Regulation of Phosphatidylinositol 3-Kinases (PI3K)/Akt

<p>LINC00958-MYC positive feedback loop modulates resistance of head and neck squamous cell carcinoma cells to chemo- and radiotherapy in vitro</p>

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