Dataset Information

Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Moreover, low expression of miR-99a-5p and miR-99a-3p significantly predicts poor prognosis in HNSCC, and these miRNAs regulate cancer cell migration and invasion. We previously showed that passenger strands of miRNAs have antitumor functions. Here, we screened miR-99a-3p-controlled oncogenes involved in HNSCC pathogenesis. Thirty-two genes were identified as miR-99a-3p-regulated genes, and 10 genes (STAMBP, TIMP4, TMEM14C, CANX, SUV420H1, HSP90B1, PDIA3, MTHFD2, BCAT1, and SLC22A15) significantly predicted 5-year overall survival. Notably, among these genes, STAMBP, TIMP4, TMEM14C, CANX, and SUV420H1 were independent prognostic markers of HNSCC by multivariate analyses. We further investigated the oncogenic function of STAMBP in HNSCC cells using knockdown assays. Our data demonstrated that the aggressiveness of phenotypes in HNSCC cells was attenuated by siSTAMBP transfection. Moreover, aberrant STAMBP expression was detected in HNSCC clinical specimens by immunohistochemistry. This strategy may contribute to the clarification of the molecular pathogenesis of this disease.

SUBMITTER: Okada R

PROVIDER: S-EPMC6953126 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma.

Okada Reona R Koshizuka Keiichi K Yamada Yasutaka Y Moriya Shogo S Kikkawa Naoko N Kinoshita Takashi T Hanazawa Toyoyuki T Seki Naohiko N

Cells 20191128 12

To identify novel oncogenic targets in head and neck squamous cell carcinoma (HNSCC), we have analyzed antitumor microRNAs (miRNAs) and their controlled molecular networks in HNSCC cells. Based on our miRNA signature in HNSCC, both strands of the miR-99a-duplex (miR-99a-5p: the guide strand, and miR-99a-3p: the passenger strand) are downregulated in cancer tissues. Moreover, low expression of miR-99a-5p and miR-99a-3p significantly predicts poor prognosis in HN ...[more]

PMID: 31795200

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Project description:BackgroundDormancy is one characteristic of cancer cells to make patients remain asymptomatic before metastasis and relapse, which is closely related to the survival rate of cancer patients, including head and neck squamous cell carcinoma (HNSCC). PRRX1 has previously been implicated in the invasion and metastasis of the epithelial-mesenchymal transition (EMT) process in different types of human carcinoma. However, whether PRRX1 can regulate cancer dormancy and its reactivation, leading to the migration and invasion of HNSCC cells, remains elusive. The aim of this study was to determine the role of PRRX1 in cellular phenotype plasticity and cancer dormancy of HNSCC cells and its association with miRNAs in HNSCC.MethodsThe expression of PRRX1 was detected by immunohistochemical staining in primary HNSCC samples and the metastatic lymph nodes. Meanwhile, the role of PRRX1 and its relationship with miR-642b-3p and EMT in cellular phenotype plasticity and cancer dormancy of HNSCC were investigated in vitro and in vivo.ResultsPRRX1 was significantly higher at the invasive front of HNSCC samples compared with the metastatic lymph nodes, and such switch process was accompanied by the cellular phenotype plasticity and cell dormancy activation. In HNSCC cell lines, PRRX1 positively promoted the expression of known EMT inducers and cooperated with activated TGF-?1 to contribute to EMT and migration and invasion of HNSCC cells. Then, we found that overexpression of miR-642b-3p, one of the most significantly downregulated miRNAs in PRRX1-overexpressed cells, significantly reduced the migration and invasion, and increased cell proliferation and apoptosis. And miR-642b-3p restoration reversed PRRX1-induced cell dormancy and EMT of HNSCC cells through TGF-?2 and p38. Finally, we demonstrated that overexpressed PRRX1 was closely correlated with miR-642b-3p downregulation and the upregulation of TGF-?2 and p38 in a xenograft model of HNSCC.ConclusionsOur findings showed that PRRX1 may be one of the main driving forces for the cellular phenotype plasticity and tumor dormancy of HNSCC. Therefore, we can raise the possibility that EMT may help to keep cancer cell in dormant state and mesenchymal-epithelial transition may resurge dormancy in HNSCC.

Dataset Information

Regulation of Oncogenic Targets by miR-99a-3p (Passenger Strand of miR-99a-Duplex) in Head and Neck Squamous Cell Carcinoma.

Publications

Regulation of Oncogenic Targets by <i>miR-99a-3p</i> (Passenger Strand of <i>miR-99a-</i>Duplex) in Head and Neck Squamous Cell Carcinoma.

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