Oncogenic miR-20b-5p contributes to malignant behaviors of breast cancer stem cells by bidirectionally regulating CCND1 and E2F1

Xia, Liqin; Feng, Li; Qiu, Jun; Feng, Zhongming; Xu, Zihan; chen, xiewan; chen, zhengtang; Sun, Junying

doi:10.21203/rs.3.rs-18259/v2

Cited by 4 publications

(6 citation statements)

References 28 publications

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“…Remarkably, previous studies have revealed that the upregulated expressions of CDK1 and CCNB1 are correlated with the worse OS in the basal subtype breast cancer, while CDC20, CCNB1, and CDK1 could act as diagnostic and prognostic markers in breast cancer. Especially, FOXM1 and E2F1 have also been demonstrated to be significantly associated with CSCs in a variety of tumors [50][51][52]. Taken together, we suggested that the mRNAsi-related genes could play very important roles in the occurrence and development as well as prognosis of the basal breast cancer patients.…”

Section: Discussionmentioning

confidence: 63%

Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer

Huang

Xie

et al. 2021

Disease Markers

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Basal breast cancer subtype is the worst prognosis subtypes among all breast cancer subtypes. Recently, a new tumor stemness index-mRNAsi is found to be able to measure the degree of oncogenic differentiation of tissues. The mRNAsi involved in a variety of cancer processes is derived from the innovative application of one-class logistic regression (OCLR) machine learning algorithm to the whole genome expression of various stem cells and tumor cells. However, it is largely unknown about mRNAsi in basal breast cancer. Here, we find that basal breast cancer carries the highest mRNAsi among all four subtypes of breast cancer, especially 385 mRNAsi-related genes are positively related to the high mRNAsi value in basal breast cancer. This high mRNAsi is also closely related to active cell cycle, DNA replication, and metabolic reprogramming in basal breast cancer. Intriguingly, in the 385 genes, TRIM59, SEPT3, RAD51AP1, and EXO1 can act as independent protective prognostic factors, but CTSF and ABHD4B can serve as independent bad prognostic factors in patients with basal breast cancer. Remarkably, we establish a robust prognostic model containing the 6 mRNAsi-related genes that can effectively predict the survival rate of patients with the basal breast cancer subtype. Finally, the drug sensitivity analysis reveals that some drug combinations may be effectively against basal breast cancer via targeting the mRNAsi-related genes. Taken together, our study not only identifies novel prognostic biomarkers for basal breast cancers but also provides the drug sensitivity data by establishing an mRNAsi-related prognostic model.

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Section: Discussionmentioning

confidence: 63%

Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer

Huang

Xie

et al. 2021

Disease Markers

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“…miR-20b-5p, a member of the tumor-related miR-106a/363 cluster, was reported to be frequently dysregulated in numerous human malignancies (9,15,35,36). Mechanistically, miR-20b-5p facilitated the proliferation and inhibited the apoptosis of breast cancer stem cells through the bidirectionally regulation of CCND1 and E2F1 (10). Conversely, miR-20b-5p was reported to inhibit migration, invasion and the cell cycle of colon cancer cells by regulating the CCND1/CDK4/FOXM1 axis (14).…”

Section: Discussionmentioning

confidence: 99%

“…The role of miR-20b-5p in human cancers is controversial. miR-20b-5p has been reported to function as an oncomiR in non-small cell lung cancer (9), breast cancer (10), gastric cancer (11), esophageal cancer (12) and laryngeal squamous cell carcinoma (13), but as a tumor-suppressor miRNA in colon cancer (14) and papillary thyroid carcinoma (15). miR-20b-5p was found to promote the tumor aggression of PCa and can predict aggressive PCa after radical prostatectomy (16,17).…”

Section: Introductionmentioning

confidence: 99%

miR-20b-5p is a novel biomarker for detecting prostate cancer

Zhai

Dou

et al. 2022

Oncol Lett

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Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific antigen (PSA) test for PCa remains controversial. Therefore, the development of more effective non-invasive biomarkers for PCa is necessary. The present study evaluated the diagnostic value of microRNA (miR)-20b-5p in PCa. Tissue miR-20b-5p expression levels and their correlation with clinical parameters were assessed using The Cancer Genome Atlas (TCGA) datasets, and the diagnostic value of the miR-20b-5p expression levels in PCa tissues was assessed using receiver operating characteristic curve analysis. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the relative expression levels of miR-20b-5p in PCa tissues compared with benign prostate hyperplasia (BPH) tissues. In addition, miR-20b-5p expression levels in PCa cell lines and non-tumorigenic prostate epithelial cells were compared. In this study, exosomes were extracted from the prostatic fluid as a source of liquid biopsy for the detection of PCa. The prostatic fluid exosomal miR-20b-5p expression levels between patients with PCa and the biopsy-negative patients were compared, and the diagnostic efficiency of prostatic fluid exosomal miR-20b-5p expression levels in PCa was compared with PSA and with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator. The mechanism by which miR-20b-5p may function in PCa was assessed using bioinformatic analysis and validation experiments. miR-20b-5p was expressed at a markedly higher level in PCa tissues compared with normal prostate tissues with high diagnostic efficiency (area under the curve: 0.826). The expression levels of miR-20b-5p were also significantly higher in PCa tissues compared with BPH tissues; similarly, miR-20b-5p was more highly expressed in PCa cells compared with non-tumorigenic prostate epithelial cells. Prostatic fluid exosomal miR-20b-5p expression levels in patients with PCa were significantly higher compared with confirmed to be biopsy-negative, and the diagnostic performance of miR-20b-5p was superior to PSA and ERSPC risk calculator. The results of RT-qPCR and western blotting following transfection of DU145 cells with miR-20b-5p mimics and inhibitor showed that miR-20b-5p reduced the expression of retinoblastoma-associated protein 1 (RB1). Therefore, RB1 may be a significant target gene for miR-20b-5p. In conclusion, the present study demonstrated that miR-20b-5p was upregulated in PCa at the tissue and cellular levels, as well as in prostatic fluid exosomes. Therefore, miR-20b-5p may be a promising early diagnostic biomarker for PCa and an important tool to guide the decision-making of prostate biopsy.

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“…Overexpression of miR-20b attenuates the proportion of cancer stem cells via the direct targeting of Oct4 and MALAT1, critical positive regulators of cancer stem cell stemness [ 73 , 81 , 102 , 103 ], and finally eases tumor regression [ 104 ]. However, miR-20b could promote breast cancer stem cell proliferation and cell cycle [ 64 ]. It indirectly elevates Cyclin D1 and E2F1 mRNA levels and promotes cell proliferation in breast cancer stem cells [ 64 ].…”

Section: Approaches To Determine the Targets Of Mir-20bmentioning

confidence: 99%

The dual role of microRNA (miR)-20b in cancers: Friend or foe?

et al. 2023

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MicroRNAs, as non-coding transcripts, modulate gene expression through RNA silencing under normal physiological conditions. Their aberrant expression has strongly associated with tumorigenesis and cancer development. MiR-20b is one of the crucial miRNAs that regulate essential biological processes such as cell proliferation, apoptosis, autophagy, and migration. Deregulated levels of miR-20b contribute to the early- and advanced stages of cancer. On the other hand, investigations emphasize the tumor suppressor ability of miR-20b. High-throughput strategies are developed to identify miR-20b potential targets, providing the proper insight into its molecular mechanism of action. Moreover, accumulated results suggest that miR-20b exerts its effects through diverse signaling pathways, including PI3K/AKT/mTOR and ERK axes. Restoration of the altered expression levels of miR-20b induces cell apoptosis and reduces invasion and migration. Further, miR-20b can be used as a biomarker in cancer. The current comprehensive review could lead to a better understanding of the miR-20b in either tumorigenesis or tumor regression that may open new avenues for cancer treatment.

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Oncogenic miR-20b-5p contributes to malignant behaviors of breast cancer stem cells by bidirectionally regulating CCND1 and E2F1

Cited by 4 publications

References 28 publications

Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer

Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer

miR-20b-5p is a novel biomarker for detecting prostate cancer

The dual role of microRNA (miR)-20b in cancers: Friend or foe?

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