Identification of core aberrantly expressed microRNAs in serous ovarian carcinoma

Chen, Steven F; Zheng, Liduan; Chaurasiya, Shyambabu; Dellinger, Thanh H.; Lü, Jianming; Wu, Xiwei; Qin, Hanjun; Wang, Jinhui; Fong, Yuman; Yuan, Yate-Ching

doi:10.18632/oncotarget.24942

Cited by 22 publications

(18 citation statements)

References 46 publications

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“…In the cellular system, the expression levels of the six miRNAs mostly are correlated with the data obtained by NGS in terms of the trends of down-regulation or up-regulation, especially for Hsa-miR-125b-1-3p, Hsa-miR-450b-3p, and Hsa-miR-1909-3p which are all upregulated in the similar fold change (~1.5 fold) from both PCR and NGS analysis in 3D culture system. Those three miRNAs are reported to be associated with regulating tumor growth [83][84][85] . For the EV RNAs data, those three miRNAs (Hsa-miR-125b-1-3p, Hsa-miR-450b-3p, and Hsa-miR-1909-3p) are also correlated very well between PCR and NGS analysis, with much higher fold change (~2-5 fold) in the 3D system.…”

Section: Resultsmentioning

confidence: 99%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Zhong

2019

Sci Rep

176

137

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For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the “gold standard”. 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D- culture derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D- culture derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D- culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D- culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

show abstract

Section: Resultsmentioning

confidence: 99%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Zhong

2019

Sci Rep

176

137

View full text Add to dashboard Cite

show abstract

“…In the cellular system, the expression levels of the six miRNAs mostly are correlated with the data obtained by NGS in terms of the trends of down-regulation or upregulation, especially for Hsa-miR-125b-1-3p, Hsa-miR-450b-3p, and Hsa-miR-1909-3p which are all upregulated in the similar fold change (~1.5 fold) from both PCR and NGS analysis in 3D culture system. Those three miRNAs are reported to be associated with regulating tumor growth [83][84][85] . For the EV RNAs data, those three miRNAs (Hsa-miR-125b-1-3p, Hsa-miR-450b-3p, and Hsa-miR-1909-3p) are also correlated very well between PCR and NGS analysis, with much higher fold change (~2-5 fold) in the 3D system.…”

Section: The 3d Cell Culture Derived Ev Rna Profile Shows a Significamentioning

confidence: 99%

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Thippabhotla

Wei

Zhong

et al. 2019

Preprint

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For studying cellular communications ex-vivo, a two-dimensional (2D) cell culture model is currently used as the "gold standard". 2D culture models are also widely used in the study of RNA expression profiles from tumor cells secreted extracellular vesicles (EVs) for tumor biomarker discovery. Although the 2D culture system is simple and easily accessible, the culture environment is unable to represent in vivo extracellular matrix (ECM) microenvironment. Our study observed that 2D culture-derived EVs showed significantly different profiles in terms of secretion dynamics and essential signaling molecular contents (RNAs and DNAs), when compared to the three-dimensional (3D) culture-derived EVs. By performing small RNA next-generation sequencing (NGS) analysis of cervical cancer cells and their EVs compared with cervical cancer patient plasma EV-derived small RNAs, we observed that 3D culture-derived EV small RNAs differ from their parent cell small RNA profile which may indicate a specific sorting process. Most importantly, the 3D culture derived EV small RNA profile exhibited a much higher similarity (~96%) to in vivo circulating EVs derived from cervical cancer patient plasma. However, 2D culture derived EV small RNA profile correlated better with only their parent cells cultured in 2D. On the other hand, DNA sequencing analysis suggests that culture and growth conditions do not affect the genomic information carried by EV secretion. This work also suggests that tackling EV molecular alterations secreted into interstitial fluids can provide an alternative, non-invasive approach for investigating 3D tissue behaviors at the molecular precision. This work could serve as a foundation for building precise models employed in mimicking in vivo tissue system with EVs as the molecular indicators or transporters. Such models could be used for investigating tumor biomarkers, drug screening, and understanding tumor progression and metastasis.

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“…Investigating along these lines, MAGI2-AS3 has been experimentally demonstrated to regulate the expression of three miRNAs-miR-15b-5p, miR-374a-5p, and miR-374b-5p that were previously associated with this lncRNA in other cancers [31][32][33]. It is indeed interesting to note that these three miRNAs that are upregulated in EOC [36] have been reported to have oncogenic roles in several other cancers [38,40,41,[49][50][51][52][53][54][55][56][57][58]. It should be mentioned that some miRNAs, for example miR-15b-5p, have been observed to have conflicting roles as both oncogenes and tumor suppressors [49,50,59].…”

Section: Discussionmentioning

confidence: 91%

“…To understand if the mechanism of action of MAGI2-AS3 with respect to these miRNAs is similar in ovarian cancer (OC), the differential expression of these three putative miRNAs (Figure 5c) between EOC and FT data used in this study [36] was analyzed, and as expected, the expression of miR-15b-5p, miR-374a-5p, and miR-374b-5p was observed to be upregulated in EOC from FT, which is in accordance with the fact that they are MAGI2-AS3 ceRNA targets.…”

Section: Magi2-as3 Acts As a Competing Endogenous Lncrna In Hgsc And mentioning

confidence: 99%

“…Differentially expressed miRNAs between high grade ovarian carcinoma and normal fallopian tissue were obtained from the study performed by Chen, et al [36]. Normalized log transformed expression data used in this study were downloaded from the Gene Expression Omnibus, GSE65819 [35] and used for the comparison of expression of hsa-miR-15b-5p, hsa-miR-374a-5p and hsa-miR-374b-5p in ovarian cancer and normal fallopian samples ( Figure 5).…”

Section: Differential Mirna Analysismentioning

confidence: 99%

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Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma

Gokulnath

Cristofaro

Manipur

et al. 2019

Cancers

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High-Grade Serous Ovarian Carcinoma (HGSC) is the most incidental and lethal subtype of epithelial ovarian cancer (EOC) with a high mortality rate of nearly 65%. Recent findings aimed at understanding the pathogenesis of HGSC have attributed its principal source as the Fallopian Tube (FT). To further comprehend the exact mechanism of carcinogenesis, which is still less known, we performed a transcriptome analysis comparing FT and HGSC. Our study aims at exploring new players involved in the development of HGSC from FT, along with their signaling network, and we chose to focus on non-coding RNAs. Non-coding RNAs (ncRNAs) are increasingly observed to be the major regulators of several cellular processes and could have key functions as biological markers, as well as even a therapeutic approach. The most physiologically relevant and significantly dysregulated non-coding RNAs were identified bioinformatically. After analyzing the trend in HGSC and other cancers, MAGI2-AS3 was observed to be an important player in EOC. We assessed its tumor-suppressive role in EOC by means of various assays. Further, we mapped its signaling pathway using its role as a miRNA sponge to predict the miRNAs binding to MAGI2AS3 and showed it experimentally. We conclude that MAGI2-AS3 acts as a tumor suppressor in EOC, specifically in HGSC by sponging miR-15-5p, miR-374a-5p and miR-374b-5p, and altering downstream signaling of certain mRNAs through a ceRNA network.

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Identification of core aberrantly expressed microRNAs in serous ovarian carcinoma

Cited by 22 publications

References 46 publications

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

3D cell culture stimulates the secretion of in vivo like extracellular vesicles

Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma

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