miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells

Mukohyama, Junko; Isobe, Taichi; Hu, Qingjiang; Hayashi, Takanori; Watanabe, Takashi; Maeda, Masao; Yanagi, Hisano; Qian, Xin; Yamashita, Kimihiro; Minami, Hironobu; Mimori, Koshi; Sahoo, Debashis; Kakeji, Yoshihiro; Suzuki, Akira; Dalerba, Piero; Shimono, Yohei

doi:10.1158/0008-5472.can-18-3544

Cited by 62 publications

(54 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Primary tumor specimens, xenograft tumors, and the liver of the PDX mice were dissociated using collagenase III (Worthington) and analyzed as previously described (Figure ) 22 . Dissociated cells were stained with mAbs conjugated to fluorescent dyes.…”

Section: Methodsmentioning

confidence: 99%

“…RNA was extracted from 100 cells sorted from breast cancer PDX and directly collected into TRIzol (Invitrogen). The expression level of 754 miRNAs was measured by multiplex semiquantitative real‐time PCR (TaqMan Array Human MicroRNA A+B Cards Set version 3.0 with Megaplex RT Primers, Human Pool Set version 3.0; Thermo Fisher Scientific) as previously described 22 . Results were normalized to RNU48 small nuclear RNA (snRNA).…”

Section: Methodsmentioning

confidence: 99%

“…We and others have shown that in epithelial malignancies such as breast cancer, self‐renewal ability of malignant cells is negatively regulated by miR‐200c, which suppresses the expression of BMI1 13,18 . In addition, miRNAs, such as let‐7, miR‐142, miR‐200c, and miR‐221, epigenetically regulate the properties of CSCs of patient‐derived tumor xenograft (PDX) cells by targeting APC , ZEB1 , and RNA‐binding protein QKI 16,20‐22 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

2020

Self Cite

View full text Add to dashboard Cite

Cancer cells with cancer stem cell (CSC) properties initiate both primary tumor formation and metastases at distant sites. Acquisition of CSC properties is highly associated with epigenetic alterations, including those mediated by microRNAs (miRNAs). We have previously established the breast cancer patient‐derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, we found that the expression levels of 3 miRNAs (miR‐25, miR‐93, and miR‐106b) in the miR‐106b‐25 cluster were much lower in the CD44+ human cancer cells metastasized to the liver than those at the primary site. Constitutive overexpression of miR‐93 suppressed invasive ability and 3D‐organoid formation capacity of breast cancer cells in vitro and significantly suppressed their metastatic ability to the liver in vivo. Wiskott‐Aldrich syndrome protein family member 3 (WASF3), a regulator of both cytoskeleton remodeling and CSC properties, was identified as a functional target of miR‐93: overexpression of miR‐93 reduced the protein level of WASF3 in breast cancer cells and WASF3 rescued the miR‐93‐mediated suppression of breast cancer cell invasion. These findings suggest that miR‐93 functions as a metastasis suppressor by suppressing both invasion ability and CSC properties in breast cancers.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…miR-221 attenuates the suppressive effect of QKI-5 on CSCs to facilitate enlargement of the CSC population and tumorigenesis. As a result, overexpression of miR-221 usually indicates poor prognosis and a reduced overall survival rate [98].…”

Section: Mir-221mentioning

confidence: 99%

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Jiao

Qian

et al. 2019

Cells

View full text Add to dashboard Cite

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments.

show abstract

“…Apart from melanoma and HCC, miR-221 was reported to be critically involved also in different cancer types, including cervical cancer [224], retinoblastoma [225], breast cancer [226], colorectal cancer [227] and gastric cancer [228].…”

Section: Microrna-221mentioning

confidence: 99%

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Linck-Paulus

Hellerbrand

Bosserhoff

et al. 2020

Cells

View full text Add to dashboard Cite

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

show abstract

miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells

Cited by 62 publications

References 22 publications

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Contact Info

Product

Resources

About