Dysregulation of SNHG16(lncRNA)-Hsa-Let-7b-5p(miRNA)-TUBB4A (mRNA) Pathway Fuels Progression of Skin Cutaneous Melanoma

作者全名："Chen, Guanghua; Yan, Jia"

作者地址："[Chen, Guanghua] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing Key Lab Child Infect & Immun,Dept Dermat, Chongqing 400014, Peoples R China; [Yan, Jia] Chongqing Med Univ, Univ Town Hosp, Digest Dept, Chongqing 401331, Peoples R China"

通信作者："Yan, J (通讯作者)，Chongqing Med Univ, Univ Town Hosp, Digest Dept, Chongqing 401331, Peoples R China."

来源：CURRENT PROTEIN & PEPTIDE SCIENCE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000903148500009

JCR分区：Q3

影响因子：2.8

年份：2022

卷号：23

期号：11

开始页：791

结束页：809

文献类型：Article

关键词：Skin cutaneous melanoma; miRNA; lncRNA; TUBB4A; DSS; PFI

摘要："Objective: Skin cutaneous melanoma(SKCM) is the most severe, and complex disease of all skin cancers. The molecular mechanisms of this cancer progression are not well understood. Methods: GEPIA online database was used to validate the differentially expressed genes from two GEO datasets. The prognostic value was calculated by the Kaplan-Meier method. RT-qPCR verified the expression of TUBB4A in SKCM cell line, and the immunohistochemistry of TUBB4A in SKCM and normal skin tissues were gained from Human Protein Atlas. Seven target prediction databases predicted potential microRNAs(miRNAs), and upstream long non-coding RNAs(lncRNAs) were predicted by starBase. The co-expressed gene of TUBB4A was obtained using the two online analysis sites UALCAN and starBase. These co-expressed genes were performed by enrichment analysis, and immune infiltration result was obtained by the TIMER2 online database. The receiver operating characteristic(ROC) curve was applied to evaluate the diagnostic value of TUBB4A in the SKCM and normal skin group. A new nomogram about TUBB4A was constructed to forecast the survival rate of SKCM patients at 1, 3, and 5 years. Results: Firstly, we found that DLL3 and TUBB4A were significantly higher expressed in skin cutaneous melanoma than normal skin. Subsequently, by analyzing progress-free interval(PFI), disease-specific survival(DSS), and disease-free survival(DFS), only TUBB4A was the most potent gene for inhibiting shin cutaneous melanoma progression. In gene ontology(GO)/ kyoto encyclopedia of genes and genomes(KEGG) analysis, TUBB4A may play a key role in the progression of skin cutaneous melanoma by regulating mitochondrial function and affecting cellular metabolism, possibly related to the immune infiltration of CD4+Th1 cells and NK cells. The upstream non-coding RNA(ncRNA) acts through the SNHG16-hsa-let-7b-5p-TUBB4A axis. Conclusion: In conclusion, we elucidated the regulatory role of the SNHG16-hsa-let-7b-5p-TUBB4A axis in the progression of skin cutaneous melanoma by modulating mitochondrial function to affect cellular metabolism. TUBB4A may be a promising diagnostic biomarker and therapeutic target for cutaneous skin melanoma."

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