title: miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression.
abstract: The development and progression of CRC are regarded as a complicated network and progressive event including genetic and/or epigenetic alterations. Recent researches revealed that MicroRNAs are biomarkers and regulators of CRC progression. Analyses of published microarray datasets revealed that miR-450b-5p was highly up-regulated in CRC tissues. In addition, high expression of miR-450b-5p was significantly associated with KRAS mutation. However, the role of miR-450b-5p in the progression of CRC remains unknown. Here, we sought to validate the expression of miR-450b-5p in CRC tissues and investigate the role and underlying mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR-450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was positively associated with poor differentiation, advanced TNM classification and poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that miR-450b-5p directly bound the 3'-UTRs of SFRP2 and SIAH1, and activated Wnt/β-Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Collectively, our work helped to understand the precise role of miR-450b-5p in the progression of CRC, and might promote the development of new therapeutic strategies against CRC.
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Ya-Ping
authors: YP
authors: Ye
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Ping
authors: P
authors: Wu
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Chun-Cai
authors: CC
authors: Gu
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Dan-Ling
authors: DL
authors: Deng
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Hong-Li
authors: HL
authors: Jiao
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Ting-Ting
authors: TT
authors: Li
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Shu-Yang
authors: SY
authors: Wang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Yong-Xia
authors: YX
authors: Wang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Zhi-Yuan
authors: ZY
authors: Xiao
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Wen-Ting
authors: WT
authors: Wei
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Yan-Ru
authors: YR
authors: Chen
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Jun-Feng
authors: JF
authors: Qiu
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Run-Wei
authors: RW
authors: Yang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Jie
authors: J
authors: Lin
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Li
authors: L
authors: Liang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Wen-Ting
authors: WT
authors: Liao
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China.
authors: Yan-Qing
authors: YQ
authors: Ding
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015398:Signal Transduction; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics*; D000098563:Seven in Absentia Proteins; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; D018631:ras Proteins; D000098563:Seven in Absentia Proteins; C000589024:MIRN450 microRNA, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins
keywords: KRAS; Wnt/β-Catenin pathway; colorectal cancer; miR-450b-5p; progression