Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy

BackgroundChemotherapeutic insensitivity remains a big challenge in prostate cancer treatment. Recently, increasing evidence has indicated that KLF4 plays a key role in prostate cancer. However, the potential biological role of KLF4 in Chemotherapeutic insensitivity of prostate cancer is still unknown.MethodsThe role of KLF4 in cisplatin-induced apoptosis was detected by western blotting and a cell counting kit (CCK8). The potential molecular mechanism of KLF4 in regulating prostate cancer chemosensitivity was investigated by RNA sequencing analysis, q-RT-PCR, western blotting and chromatin immunoprecipitation (ChIP). The expression level of KLF4 mediated by miR-32-5p was confirmed by bioinformatic analysis and luciferase assays.ResultsHere, we found that KLF4 was induced by cisplatin in prostate cancer cells and that the increase in KLF4 promoted cell apoptosis. Further mechanistic studies revealed that KLF4 directly bound to the promoter of BIK, facilitating its transcription. Additionally, we also found that the gene encoding KLF4 was a direct target of miR-32-5p. The downregulation of miR-32-5p in response to cisplatin treatment promoted KLF4 expression, which resulted in a increase in the chemosensitivity of prostate cancer.ConclusionThus, our data revealed that KLF4 is an essential regulator in cisplatin-induced apoptosis, and the miR-32-5p-KLF4-BIK signalling axis plays an important role in prostate cancer chemosensitivity.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0270-x) contains supplementary material, which is available to authorized users.

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“…Relative Renilla luciferase activity was normalized to firefly luciferase activity. The assay was performed as previously described [22, 23]. …”

Section: Methodsmentioning

confidence: 99%

KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer

Zhang

Chao

et al. 2018

Cell Commun Signal

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“…Similarly, ATG7 deficiency promoted apoptosis of human esophageal squamous cell carcinoma cells [16]. Inhibition of ATG5 enhanced cisplatin induced apoptosis and decreased cell viability according to a recent study by Ma et al [8] Zhao et al suggested that silencing of ATG14 caused higher apoptosis rates in sensitizing osteosarcoma cells to cisplatin [13]. These results indicate that ATG14 is capable of promoting chemoresistance of cancer cells.…”

Section: Discussionmentioning

confidence: 90%

“…Long non-coding RNAs (lncRNAs, >200 nt), play a critical role in biological processes, such as cell proliferation, differentiation, apoptosis, and migration [7,8]. Various lncRNAs, such as HOTTIP, MEG3, UCA1 and MALAT1, have been demonstrated to be involved in different carcinomas including MM [9].…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Yang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells. Methods: Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells. Results: The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells. Conclusion: Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.

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“…6 Inconsequently, suppressing of autophagy enhances drug resistance in gastric cancer cells. 4,11 A previous study found that blocking autophagy increased chemosensitivity to cisplatin in glioma. 10 However, several lines of research have confirmed the protective roles of autophagy in glioma cell growth during chemotherapy.…”

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confidence: 99%

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

Huo

Chen

2018

J of Cellular Biochemistry

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Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest‐specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy‐related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin‐inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5‐mediated depression in cisplatin‐evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5‐increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.

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Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy

Cited by 57 publications

References 31 publications

KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer

KLF4, a miR-32-5p targeted gene, promotes cisplatin-induced apoptosis by upregulating BIK expression in prostate cancer

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

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