Dataset Information

Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1.

ABSTRACT:

Objective

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) could mediate the malignancy of tumor cells by transmitting targeted cargo. Therein, this study intends to explore the function of BMSC-Exos transmitting microRNA-425 (miR-425)/cytoplasmic polyadenylation binding protein 1 (CPEB1) in lung cancer growth.

Methods

miR-425 and CPEB1 levels in cancer tissues and cells were measured. BMSCs and their exosomes were collected and identified. After intervention with BMSC-Exos, miR-425 or CPEB1, invasion and migration of A549 and NCI-H1299 cells in vitro, and lung metastasis of A549 cells in vivo were observed. The relationship between miR-425 and CPEB1 was verified.

Results

miR-425 was highly expressed while CPEB1 was lowly expressed in lung cancer tissues of patients. CPEB1 was the direct target of miR-425. Down-regulating miR-425 or up-regulating CPEB1 decreased cell invasion and migration ability of A549 and NCI-H1299 cells, as well as decreased the number of lung metastasis lesions in vivo. After co-culture with BMSC-Exos, A549 and NCI-H1299 cells showed promoted migration and invasion in vitro and A549 cells demonstrated increased lung metastasis in vivo. Down-regulated miR-425 or up-regulated CPEB1 reversed the promotion of BMSC-Exos on lung cancer cell invasion, migration and lung metastasis.

Conclusion

BMSC-Exos could deliver miR-425 to inhibit CPEB1 expression in lung cancer cells, thereby promoting the malignant biological properties of lung cancer cells and their metastasis in vivo.

SUBMITTER: Wang G

PROVIDER: S-EPMC9061616 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1.

Wang Guoqiang G Ji Xiuli X Li Pan P Wang Wei W

Regenerative therapy 20220425

<h4>Objective</h4>Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) could mediate the malignancy of tumor cells by transmitting targeted cargo. Therein, this study intends to explore the function of BMSC-Exos transmitting microRNA-425 (miR-425)/cytoplasmic polyadenylation binding protein 1 (CPEB1) in lung cancer growth.<h4>Methods</h4>miR-425 and CPEB1 levels in cancer tissues and cells were measured. BMSCs and their exosomes were collected and identified. After intervention with BM ...[more]

PMID: 35582707

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Project description:BackgroundMetastasis is the leading cause of death among patients with colorectal cancer (CRC). Therefore, it is important to explore the molecular mechanisms of metastasis to develop effective therapeutic targets for CRC. In the present study, ribosomal protein L21 (RPL21) was considered as being involved in promoting CRC metastasis, yet the underlying mechanism requires further investigation.MethodsImmunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction were performed to measure the expression of RPL21 and lysosome-associated membrane protein 3 (LAMP3) in CRC tissues and cells. Wound healing, transwell migration, and invasion assays were performed to study the migration and invasion of cultured CRC cells. An orthotopic CRC mouse model was developed to investigate the metastatic ability of CRC. Transcriptome sequencing was conducted to identify the genes related to RPL21. The dual-luciferase reporter gene assay was performed to determine the transcriptional activity of transcription factor EB (TFEB). The GST/His pull-down assay was performed to investigate the specific binding sites of RPL21 and LAMP3. The cell adhesion assay was performed to determine the adhesion ability of CRC cells. Immunofluorescence staining was performed to observe focal adhesions (FAs).ResultsRPL21 was highly expressed in CRC, contributing to tumor invasiveness and poor patient prognosis. Functionally, RPL21 promoted the migration and invasion of CRC cells in vitro and tumor metastasis in vivo. Moreover, LAMP3 was identified as being highly related to RPL21 and was essential in promoting the migration and invasion of CRC cells. Mechanistically, RPL21 activated the transcriptional function of TFEB to upregulate LAMP3 expression. RPL21 directly bound to the aa 341-416 domain of LAMP3 via its aa 1-40 and aa 111-160 segments. The combination of RPL21 and LAMP3 enhanced the stability of the RPL21 protein by suppressing the degradation of the ubiquitin-proteasome system. Furthermore, RPL21 and LAMP3 promoted the formation of immature FAs by activating the FAK/paxillin/ERK signaling pathway.ConclusionsRPL21 promoted invasion and metastasis by regulating FA formation in a LAMP3-dependent manner during CRC progression. The interaction between RPL21 and LAMP3 may function as a potential therapeutic target against CRC.

Dataset Information

Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1.

Objective

Methods

Results

Conclusion

Publications

Human bone marrow mesenchymal stem cell-derived exosomes containing microRNA-425 promote migration, invasion and lung metastasis by down-regulating CPEB1.

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