Infrequently expressed miRNAs in colorectal cancer tissue and tumor molecular phenotype

Slattery, Martha L.; Lee, Frances Y.; Pellatt, Andrew J.; Mullany, Lila E.; Stevens, John R.; Samowitz, Wade S.; Wolff, Roger K.; Herrick, Jennifer S.

doi:10.1038/modpathol.2017.38

Cited by 20 publications

(15 citation statements)

References 54 publications

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“…It is interesting that multiple miRNAs were discovered to be present in 3D cell-derived EVs as well as the cervical cancer patient plasma-derived EVs, but not in 2D-culture derived EVs. A few of these miRNAs, such as miRNA-2277, miRNA-3691, miRNA-4488, miRNA-548ao, miRNA-6871, miRNA-93, miRNA-4763, miRNA-6751, and miRNA-4633-5p, have been highly associated with control of stability and translation of mRNA [80][81][82] . To explore the miRNA pathways significantly enriched in EVs from their parent cells, we performed an over-representation analysis (ORA) of two groups of miRNAs with a fold change threshold of 10 (i.e.…”

Section: Resultsmentioning

confidence: 99%

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

Thippabhotla

Zhong

2019

Sci Rep

174

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.

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Section: Resultsmentioning

confidence: 99%

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

Thippabhotla

Zhong

2019

Sci Rep

174

137

View full text Add to dashboard Cite

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“…XUEYAN WEN 1-3* , SONGRONG LI 1,2* , MENGCHAN GUO 1,2* , HONGZHAN LIAO [1][2][3] , YONGMIN CHEN 1,2 , XI KUANG 1,2 , XIAOPING LIAO 1,2 , LIN MA 1,2 and QIFU LI 1,2 non-coding RNA sequences, typically 19-25 nucleotides in length, first identified in 1993 (5). As important regulatory factors, miRNAs participate in cell proliferation, differentiation, apoptosis, cell cycle progression and other biological processes, playing vital regulatory roles in biological development and tumorigenesis (6).…”

Section: Mir-181a-5p Inhibits the Proliferation And Invasion Of Drug-mentioning

confidence: 99%

miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

Wen

Guo

et al. 2020

Oncol Lett

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Glioblastoma (GBM) is the most common malignant primary tumor in the human central nervous system. The present study aimed to explore the molecular mechanism by which microRNA (miR)-181a-5p targets the F-box protein 11 (FBXO11) in glioma cells to inhibit cell proliferation and invasion. Reverse transcription-quantitative (RT-q)PCR was performed to detect the expression levels of miR-181a-5p in U251TR cells, U251 cells, primary GBM tissues and relapsed GBM tissues in order to determine the association between miR-181a-5p and the chemoresistance of GBM cells. The expression levels of miR-181a-5p in GBM cells were modulated via transfecting miR-181a-5p mimics and inhibitors. Cell Counting Kit-8 assays were undertaken to assess the effects of miR-181a-5p on drug sensitivity and proliferation of GBM cells. Wound healing assays were performed to examine the effects of miR-181a-5p on the migratory ability of GBM cells. Furthermore, the effects of miR-181a-5p on the invasive ability of GBM cells were analyzed using an in vitro invasion assay. Flow cytometry analysis was carried out to determine whether overexpression of miR-181a-5p can promote the apoptotic rate of GBM cells. RT-qPCR and western blotting were employed to detect the effects of miR-181a-5p on mRNA and protein expression of FBX011. miR-181a-5p exhibited low expression in resistant GBM cell lines and recurrent tumor tissues. Dual-luciferase reporter assays were utilized to detect luciferase activity to verify the targeted regulatory association between miR-181a-5p and FBXO11. Upregulation of miR-181a-5p promoted the sensitivity of GBM cells to temozolomide (TMZ), increased the apoptotic rate of GBM cells and significantly inhibited the invasive and migratory capacities of GBM cells. In drug-resistant glioma cells, compared with the miR-negative control group and the blank group, the expression of miR-181a-5p was significantly upregulated (P<0.01), while the expression of FBXO11 protein was downregulated. miR-181a-5p increased the sensitivity of GBM cells to TMZ. miR-181a-5p significantly inhibited the migratory and invasive capacities of GBM cells. miR-181a-5p may become a novel effective target for the treatment of GBM. The results of dual-luciferase reporter assays indicated that miR-181a-5p could target the 3'-untranslated region of FBXO11. The underlying mechanism may be targeted inhibition of FBXO11 gene expression, or may be associated with apoptosis.

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“…While we detected some associations between survival and any expression of a few miRNAs, [ 11 ] it is possible that other infrequently expressed miRNAs are important only if expressed at higher levels. We have previously shown that infrequently expressed miRNAs are useful in distinguishing specific tumor molecular phenotypes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Infrequently expressed miRNAs influence survival after diagnosis with colorectal cancer

et al. 2017

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Half of miRNAs expressed in colorectal tissue are expressed < 50% of the population. Many infrequently expressed miRNAs have low levels of expression. We hypothesize that less frequently expressed miRNAs, when expressed at higher levels, influence both disease stage and survival after diagnosis with colorectal cancer (CRC); low levels of expression may be background noise.We examine 304 infrequently expressed miRNAs in 1893 population-based cases of CRC with paired carcinoma and normal mucosa miRNA profiles. We evaluate miRNAs with disease stage and survival after adjusting for age, study center, sex, MSI status, and AJCC stage. These miRNAs were further evaluated with RNA-Seq data to identify miRNA::mRNA associations that may provide insight into the functionality of miRNAs.Eleven miRNAs were associated with advanced disease stage among colon cancer patients (Q value = 0.10). Eight infrequently expressed miRNAs influenced survival if highly expressed in overall CRC. Of these, five increased likelihood of dying if they were highly expressed, i.e. miR-124-3p, miR-143-5p, miR-145-3p, miR31-5p, and miR-99b-5p, while three were associated with better survival if highly expressed, i.e. miR-362-5p, miR-374a-5p, and miR-590-5p. Thirteen miRNAs infrequently expressed in colon-specific carcinoma tissue were associated with CRC survival if highly expressed. Evaluation of miRNAs::mRNA associations showed that mRNA expression influenced by infrequently expressed miRNA contributed to networks and pathways shown to influence disease progression and prognosis.Our large study enabled us to examine the implications of infrequently expressed miRNAs after removal of background noise. These results require replication in other studies. Confirmation of our findings in other studies could lead to important markers for prognosis.

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Infrequently expressed miRNAs in colorectal cancer tissue and tumor molecular phenotype

Cited by 20 publications

References 54 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

miR‑181a‑5p inhibits the proliferation and invasion of drug‑resistant glioblastoma cells by targeting F‑box protein 11 expression

Infrequently expressed miRNAs influence survival after diagnosis with colorectal cancer

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