Background Very few proteins encoded by the presumed non-coding RNA transcripts have been identified. Their cellular functions remain largely unknown. This study identifies the tumor-suppressor function of a novel microprotein encoded by the precursor of miR-34a. It consists of 133 amino acid residues, thereby named as miPEP133 (pri-microRNA encoded peptide 133). Methods We overexpressed miPEP133 in nasopharyngeal carcinoma (NPC), ovarian cancer and cervical cancer cell lines to determine its effects on cell growth, apoptosis, migration, or invasion. Its impact on tumor growth was evaluated in a xenograft NPC model. Its prognostic value was analyzed using NPC clinical samples. We also conducted western blot, immunoprecipitation, mass spectrometry, confocal microscopy and flow cytometry to determine the underlying mechanisms of miPEP133 function and regulation. Results miPEP133 was expressed in normal human colon, stomach, ovary, uterus and pharynx. It was downregulated in cancer cell lines and tumors. miPEP133 overexpression induced apoptosis in cancer cells and inhibited their migration and invasion. miPEP133 inhibited tumor growth in vivo. Low miPEP133 expression was an unfavorable prognostic marker associated with advanced metastatic NPC. Wild-type p53 but not mutant p53 induced miPEP133 expression. miPEP133 enhanced p53 transcriptional activation and miR-34a expression. miPEP133 localized in the mitochondria to interact with mitochondrial heat shock protein 70kD (HSPA9) and prevent HSPA9 from interacting with its binding partners, leading to the decrease of mitochondrial membrane potential and mitochondrial mass. Conclusion miPEP133 is a tumor suppressor localized in the mitochondria. It is a potential prognostic marker and therapeutic target for multiple types of cancers.

In recent years, the repurposing of conventional and chemotherapeutic drugs is recognized as an alternative strategy for health care. The main purpose of this study is to strengthen the application of non‐oncological drug metformin on breast cancer treatment in the perspective of epigenetics. In the present study, metformin was found to inhibit cell proliferation, promote apoptosis and induce cell cycle arrest in breast cancer cells at a dose‐dependent manner. In addition, metformin treatment elevated acH3K9 abundance and decreased acH3K18 level. The expression of lncRNA MALAT1, HOTAIR, DICER1‐AS1, LINC01121 and TUG1 was up‐regulated by metformin treatment. In metformin‐treated cells, MALAT1 knock‐down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression. The expression of Beclin1, VDAC1, LC3‐II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock‐down. The reduced phosphorylation of c‐Myc was further decreased in the metformin‐treated cells in combination with MALAT1 knock‐down than metformin treatment alone. Taken together, these results provide a promising repurposed strategy for metformin on cancer treatment by modulating epigenetic modifiers.

BackgroundThe purpose of our study was to investigate the functional role of microRNA-340 (miR-340) in endometrial carcinoma (EC).Material/MethodsHuman EC cell line RL 95-2 was transfected with miR-340 mimics, inhibitors, or controls. After 48 h of transfection, the cell viability was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay. The BrdU assay and apoptosis assay were performed to determine the effects of miR-340 mimics or inhibitors on cell proliferation and apoptosis, respectively. The underlying mechanisms involved in cell proliferation and apoptosis were explored by measuring the protein levels of cell cycle regulators (p27 kinase inhibition protein (KIP) 1 and p21) and apoptosis-related factors (B-cell lymphoma-2 (Bcl-2), Bax, pro-Caspase 3, and active-Caspase-3).ResultsOverexpression of miR-340 significantly inhibited the cell viability (P<0.05) and cell proliferation (P<0.01) of RL 95-2 cells compared with the control group, but increased the apoptosis (P<0.01). However, suppression of miR-340 had opposite results. Moreover, the protein levels of p27 KIP1, Bax, pro-Caspase 3, and active-Caspase-3 were significantly increased by overexpression of miR-340 but were statistically decreased by suppression of miR-340. Contrary results were found in the protein levels of Bcl-2. However, no significant differences were found in p21 expression.ConclusionsMiRNA-340 acts as an anti-oncogene in EC cell line RL 95-2 by inhibition of tumor cell proliferation and induction of apoptosis.

The aim of the present study was to identify genes associated with and the underlying mechanisms in nasopharyngeal carcinoma (NPC) using microarray data. GSE12452 and GSE34573 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. GEO2R was utilized to obtain differentially expressed genes (DEGs). In addition, the Database for Annotation, Visualization and Integrated Discovery was used to perform pathway enrichment analyses for DEGs using the Gene Ontology (GO) annotation along with the Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, Cytoscape was used to perform module analysis of the protein-protein interaction (PPI) network and pathways of the hub genes were studied. A total of 298 genes were ascertained as DEGs in the two datasets. To functionally categorize these DEGs, we obtained 82 supplemented GO terms along with 7 KEGG pathways. Subsequently, a PPI network consisting of 10 hub genes with high degrees of interaction was constructed. These hub genes included cyclin-dependent kinase (CDK) 1, structural maintenance of chromosomes (SMC) 4, kinetochore-associated (KNTC) 1, kinesin family member (KIF) 23, aurora kinase A (AURKA), ATAD (ATPase family AAA domain containing) 2, NDC80 kinetochore complex component, enhancer of zeste 2 polycomb repressive complex 2 subunit, BUB1 mitotic checkpoint serine/threonine kinase and protein regulator of cytokinesis 1. CDK1, SMC4, KNTC1, KIF23, AURKA and ATAD2 presented with high areas under the curve in receiver operator curves, suggesting that these genes may be diagnostic markers for nasopharyngeal carcinoma. In conclusion, it was proposed that CDK1, SMC4, KNTC1, KIF23, AURKA and ATAD2 may be involved in the tumorigenesis of NPC. Furthermore, they may be utilized as molecular biomarkers in early diagnosis of NPC.