The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Zhang, Huilin; Lü, Bingjian

doi:10.3390/cancers12102926

Cited by 31 publications

(16 citation statements)

References 181 publications

(222 reference statements)

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“…In this study, we found that exosomes of OS-chemoresistant cells could induce autophagy of OSC. It has been reported that autophagy was one of important way to lead to drug resistance [21]. In our study, miR-331 could lead to autophagy of OSC while inhibition of miR-331 could suppress autophagy of OSC.…”

Section: Discussionmentioning

confidence: 50%

Exosomal miR-331 from Chemoresistant Osteosarcoma Cells induced Chemoresistance through Autophagy

Zhao¹,

Zhao²,

Liu

et al. 2021

Preprint

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BackgroundOsteosarcoma (OS) is a highly malignant tumor. Improving chemotherapeutic resistance is very important to improve the survival rate of OS. Exosomes and microRNAs (MiRNA) play important roles in the mechanism of chemotherapeutic resistance transmission. More and more researches focus the mechanism of miRNAs carried by exosomes in the transmission of chemotherapeutic resistance of OS. This study focused on exploring the mechanism of exosomal miR-331 in the transmission of chemoresistance in OS.MethodsWe cultured OS drug-resistant cells and extracted exosomes of these cells. The secretion and uptake of exosomes in OS drug-resistant cells and OS cells (OSCs) were confirmed by fluorescence tracking assay and transwell experiments. The differential expression of microRNA-331 (miR-331) in exosomes of OS resistant and OS cells was investigated by RT-PCR. The effects of drug-resistant exosomes on proliferation and migration of OS cells were determined by MTT assay and scratches assay. MDC staining, RT-PCR, and Western blot were used to detect the role of autophagy which regulated by drug-resistant cell-derived exosom-miR-331.ResultsWe found that the expression difference of miR-331 between MG63/CDDP and MG63 was the most significant. Drug resistant OSCs secreted exosomes and were ingested by OSCs, which then promoted OSCs to acquire drug resistance. In addition, exosomes secreted by drug-resistant OSCs promote drug resistance by carrying miRNAs. Interestingly, inhibition of miRNA resulted in reduced drug resistance transmission of exosomes. Finally, we found that the exosomes secreted by drug-resistant OSCs could induce autophagy of OSCs by carrying miR-331, thus making OSCs acquire drug resistance. Inhibition of miR-331 can effectively improve drug resistance of OSCs.ConclusionsChemoresistant OSCs-derived exosomes promote the transmission of drug resistance by carrying miR-331 and inducing autophagy. Inhibition of miR-331 could effectively alleviate drug resistance of OSCs.

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Section: Discussionmentioning

confidence: 50%

Exosomal miR-331 from Chemoresistant Osteosarcoma Cells induced Chemoresistance through Autophagy

Zhao¹,

Zhao²,

Liu

et al. 2021

Preprint

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“…Generally, lncRNAs located in the nucleus directly bind to proteins and control gene expression at the transcriptional level (34). By contrast, cytoplasmic lncRNAs serve as endogenous decoys for miRNAs through sequence complementarity, thereby influencing gene expression and signal transduction pathways at the posttranscriptional level (35). Consequently, the actions of lncRNAs are determined by their unique subcellular localizations.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA ZSCAN16‑AS1 promotes the malignant properties of hepatocellular carcinoma by decoying microRNA‑451a and consequently increasing ATF2 expression

Lv¹,

Wan²,

Shen³

et al. 2021

Mol Med Rep

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The importance of long noncoding RNAs (lncRNAs) in the oncogenicity of hepatocellular carcinoma (HCC) has been widely studied. However, the detailed functions of ZSCAN16 antisense RNA 1 (ZSCAN16-AS1) have seldom been explored in HCC until the present study. In the present study, experiments were performed to clarify whether ZSCAN16-AS1 is implicated in the oncogenesis and progression of HCC and to explore the possible underlying mechanisms. ZSCAN16-AS1 expression was analyzed using reverse transcription-quantitative PCR. The effects of ZSCAN16-AS1 on the biological behavior of HCC cells were demonstrated by functional experiments. The direct binding capacity of ZSCAN16-AS1 with microRNA-451a (miR-451a) was indicated by the luciferase reporter assay and RNA immunoprecipitation. The high expression of ZSCAN16-AS1 was confirmed in HCC by The Cancer Genome Atlas database and the cohort of the present study. Survival data revealed that patients with a high ZSCAN16-AS1 level had worse prognosis compared with those with a low ZSCAN16-AS1 level. Following ZSCAN16-AS1 knockdown, HCC cell proliferation, migration and invasion were curbed, whereas cell apoptosis was promoted in vitro. The absence of ZSCAN16-AS1 restricted tumor growth of HCC cells in vivo. Mechanistically, ZSCAN16-AS1 acted as a competing endogenous RNA by decoying miR-451a in HCC cells. Furthermore, activating transcription factor 2 (ATF2), a direct target of miR-451a, was under the regulation of ZSCAN16-AS1, which was exerted by sequestering miR-451a. In addition, miR-451a knockdown or ATF2 resumption reversed the proliferation suppression, apoptosis promotion and migration and invasion inhibition triggered by ZSCAN16-AS1 silencing. In conclusion, ZSCAN16-AS1, a pro-oncogenic lncRNA, aggravated the malignancy of HCC by controlling the miR-451a/ATF2 axis. An understanding of the competing endogenous RNA network of ZSCAN16-AS1/miR-451a/ATF2 in HCC might be instrumental in the development of attractive targets for molecular therapy.

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“…Первая связана с аутофагией -катаболическим процессом, при котором органеллы разрушаются лизосомами, когда клетки подвергаются клеточному стрессу [5,43]. Согласно данным литературы, активация аутофагии может способствовать химиорезистентности опухоли [43][44][45][46]. Недавние исследования продемонстрировали, что ОП-индуцированная аутофагия посредством активации пути ОП / NF-κB способствует химиорезистентности к гемцитабину в опухолевых клетках при раке поджелудочной железы [47,48].…”

Section: остеопонтин и эпителиально-мезенхимальный переходunclassified

“…При подавлении экспрессии ОП с помощью лентивирусной трансфекции цитотоксическое действие гемцитабина на клетки рака поджелудочной железы усиливалось [47]. В ряде исследований показано, что резистентность клеток гепатоцеллюлярной карциномы к эпирубицину и цисплатину была вызвана тем, что ОП стимулировал аутофагию и выживание опухолевых клеток путем связывания с его рецепторным интегрином αvβ3, тем самым поддерживая фенотип, подобный стволовым опухолевым клеткам [44][45][46][47][48][49][50].…”

Section: остеопонтин и эпителиально-мезенхимальный переходunclassified

Prognostic and predictive significance of osteopontin in malignant neoplasms

Zubareva

Сеньчукова

2021

Usp. mol. onkol

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Osteopontin is an extracellular matrix protein which is produced by different types of cells and plays an important functional role in many biological processes. This review discusses the main functions of osteopontin, its role in the progression and chemoresistance of malignant neoplasms, in the regulation of epithelial-mesenchymal transition, angiogenesis, and the body’s immune response to the tumor. The article considers the currently known mechanisms by which osteopontin affects to the survival, mobility and invasion of tumor cells, to tumor sensitivity to drug treatment, as well as the prospects for a integrated study of the predictive significance of osteopontin, markers of hypoxia, angiogenesis, epithelial- mesenchymal transition, and immunological tolerance.

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The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Cited by 31 publications

References 181 publications

Exosomal miR-331 from Chemoresistant Osteosarcoma Cells induced Chemoresistance through Autophagy

Exosomal miR-331 from Chemoresistant Osteosarcoma Cells induced Chemoresistance through Autophagy

Long non‑coding RNA ZSCAN16‑AS1 promotes the malignant properties of hepatocellular carcinoma by decoying microRNA‑451a and consequently increasing ATF2 expression

Prognostic and predictive significance of osteopontin in malignant neoplasms

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