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MicroRNA-23b Plays ...
MicroRNA-23b Plays a Tumor-Suppressive Role in Cutaneous Squamous Cell Carcinoma and Targets Ras-Related Protein RRAS2
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- Sun, Chengxi (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Clin Lab, Jinan, Peoples R China.
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- Das Mahapatra, Kunal (author)
- Karolinska Institutet
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- Elton, Jonathan (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Dept Med, Unit Dermatol & Venerol, Stockholm, Sweden.
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- Li, Chen (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Fernando, Winnie (author)
- Karolinska Inst, Dept Med, Unit Dermatol & Venerol, Stockholm, Sweden.
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- Lohcharoenkal, Warangkana (author)
- Karolinska Inst, Dept Med, Unit Dermatol & Venerol, Stockholm, Sweden.
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- Lapins, Jan (author)
- Karolinska Univ Hosp, Unit Dermatol, Stockholm, Sweden.
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- Homey, Bernhard (author)
- Univ Hosp Duesseldorf, Heinrich Heine Univ, Med Fac, Dept Dermatol, Dusseldorf, Germany.
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- Sonkoly, Enikö (author)
- Uppsala universitet,Dermatologi och venereologi,Karolinska Inst, Dept Med, Unit Dermatol & Venerol, Stockholm, Sweden.;Karolinska Univ Hosp, Unit Dermatol, Stockholm, Sweden.
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- Pivarcsi, Andor (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Dermatologi och venereologi,Karolinska Inst, Dept Med, Unit Dermatol & Venerol, Stockholm, Sweden.
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- English.
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In: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 143:12, s. 2386-2396
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Abstract
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- Cutaneous squamous cell carcinoma (cSCC) is one of the most common types of cancer with metastatic potential. MicroRNAs regulate gene expression at the post-transcriptional level. In this study, we report that miR23b is downregulated in cSCCs and in actinic keratosis and that its expression is regulated by the MAPK signaling pathway. We show that miR-23b suppresses the expression of a gene network associated with key oncogenic pathways and that the miR-23b-gene signature is enriched in human cSCCs. miR-23b decreased the expression of FGF2 both at mRNA and protein levels and impaired the angiogenesis-inducing ability of cSCC cells. miR23b overexpression suppressed the capacity of cSCC cells to form colonies and spheroids, whereas the CRISPR/Cas9-mediated deletion of MIR23B resulted in increased colony and tumor sphere formation in vitro. In accordance with this, miR-23b-overexpressing cSCC cells formed significantly smaller tumors upon injection into immunocompromised mice with decreased cell proliferation and angiogenesis. Mechanistically, we verify RRAS2 as a direct target of miR-23b in cSCC. We show that RRAS2 is overexpressed in cSCC and that interference with its expression impairs angiogenesis and colony and tumorsphere formation. Taken together, our results suggest that miR-23b acts in a tumor-suppressive manner in cSCC, and its expression is decreased during squamous carcinogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Publication and Content Type
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- art (subject category)
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- By the author/editor
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Sun, Chengxi
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Das Mahapatra, K ...
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Elton, Jonathan
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Li, Chen
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Fernando, Winnie
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Lohcharoenkal, W ...
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Lapins, Jan
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Homey, Bernhard
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Sonkoly, Enikö
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Pivarcsi, Andor
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Uppsala University
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Karolinska Institutet