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miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6

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Abstract

Tumor-derived extracellular vesicles (EVs) promote ovarian cancer (OC) metastasis by carrying microRNAs (miRs). This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was performed to verify the mechanism of EVs-miR-106a-5p and KLF6 in OC metastasis. Consequently, miR-106a-5p was enhanced in OC and correlated with OC metastasis. SKOV3-EVs promoted the proliferation, migration, and invasion of OC cells. Mechanistically, EVs carried miR-106a-5p into other OC cells, inhibited KLF6, reduced the binding of KLF6 to the PTTG1 promoter, and upregulated PTTG1 transcription. Overexpression of KLF6 or silencing of PTTG1 attenuated the promoting effect of EVs-miR-106a-5p on OC cells. EVs-miR-106a-5p facilitated OC metastasis via the KLF6/PTTG1 axis. To conclude, OC cell-derived EVs facilitated the progression and metastasis of OC via the miR-106a-5p/KLF6/PTTG1 axis.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

OC:

Ovarian cancer

EVs:

Extracellular vesicles

miRs:

MicroRNAs

KLF6:

Krüppel-like factor 6

PTTG1:

Pituitary tumor transforming gene 1

FBS:

Fetal bovine serum

PBS:

Phosphate-buffered saline

BCA:

Bicinchoninic acid

NTA:

Nanoparticle tracking analysis

TEM:

Transmission electron microscope

RIPA:

Radio-immunoprecipitation assay

MOI:

Multiplicity of infection

CCK-8:

Cell counting kit-8

WT:

Wild-type

MUT:

Mutant

RIP:

RNA immunoprecipitation

ChIP:

Chromatin immunoprecipitation

HE:

Hematoxylin and eosin

RT-qPCR:

Reverse transcription quantitative polymerase chain reaction

TBST:

Tris-buffered saline-tween

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81670557) and National Key Research and Development Program of China, 2016YFC1000700, 2016YFC1000703.

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Authors and Affiliations

  1. Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, 710004, Shaanxi, China

    Yunyun Zheng & Guihu Wang

  2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of AFM (Air Force Medical University), Xi’an, 710032, Shaanxi, China

    Yunyun Zheng

  3. Department of Obstetrics and Gynecology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, 710004, Shaanxi, China

    Kang Zhu

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  1. Yunyun Zheng
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  2. Kang Zhu
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  3. Guihu Wang
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Contributions

YYZ contributed to the conception, KZ completed the experiments. YYZ and KZ drafted the manuscript, GHW critically revised the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Guihu Wang.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study got the approval of the Ethics Committee of Xi'an Jiaotong University Second Affiliated Hospital (S2016-120-02), following the Declaration of Helsinki. The informed consent was conferred by each eligible participant. This study was approved by the Ethical Committee of Xi'an Jiaotong University Second Affiliated Hospital (2016127) and the animals were treated on the basis of the standards of animal ethics.

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Zheng, Y., Zhu, K. & Wang, G. miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6. Clin Exp Metastasis 39, 603–621 (2022). https://doi.org/10.1007/s10585-022-10165-8

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