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FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p).


ABSTRACT: Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of miR-99a (miR-99a-5p and miR-99a-3p) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced miR-99a-5p or miR-99a-3p expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): p = 0.1264 and 0.0316; overall survival (OS): p = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre-miR-99a in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: p < 0.05). Notably, FAM64A was regulated by both miR-99a-5p and miR-99a-3p in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: p = 0.0175; DFS: p = 0.0276). FAM64A knockdown using siRNAs suggested that elevated FAM64A expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.

SUBMITTER: Mizuno K 

PROVIDER: S-EPMC7564711 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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<i>FAM64A</i>: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of <i>miR-99a</i> (<i>miR-99a-5p</i> and <i>miR-99a-3p</i>).

Mizuno Keiko K   Tanigawa Kengo K   Nohata Nijiro N   Misono Shunsuke S   Okada Reona R   Asai Shunichi S   Moriya Shogo S   Suetsugu Takayuki T   Inoue Hiromasa H   Seki Naohiko N  

Cells 20200911 9


Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of <i>miR-99a</i> (<i>miR-99a-5p</i> and <i>miR-99a-3p</i>) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced <i>miR-99a-5p</i> or <i>miR-99a-3p</i> expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): <i>p</i>  ...[more]

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