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BackgroundCervical cancer is one of the most common malignancies in women, leading to major health problems for its high morbidity and mortality. Numerous studies have demonstrated that circular RNAs (circRNAs) could be participated in the progression of multifarious diseases, especially plentiful carcinomas. CircAMOTL1 (angiomotin-like1, ID: hsa_circ_0004214), which is located on human chromosome 11:9 4532555-94533477, is involved in the occurrence of breast cancer, etc. However, the intrinsic and concrete molecular mechanism of circAMOTL1 in cervical carcinomas remained thoroughly unclear, which was also the bottleneck of circRNAs studies in cancer.MethodsThe relative expression levels of circAMOTL1 and miR-526b in cervical carcinoma patients’ specimens and cervical carcinoma cell lines were detected by RT-qPCR. Through experiments including loss-function and overexpression, the biological effects of circAMOTL1 and miR-526b on the proliferation, migration, apoptosis, and tumorigenicity were explored in cervical carcinomas. Dual luciferase reporter gene analysis, western blot, and other methods were adopted to explore the circAMOTL1 potential mechanism in cervical carcinomas.ResultsIn our experiments, our researches displayed that circAMOTL1 was significantly higher expression in cervical carcinomas specimens and cell lines. Further experiments illustrated that the knockdown of circAMOTL1 could restrain the malignant phenotype, AKT signaling, and epithelial–mesenchymal transition (EMT) of in cervical carcinomas cells. Meanwhile miR-526b was downregulated in cervical carcinomas and even miR-526b could partially reverse circAMOTL1 function in malignant cervical tumor cells. CircAMOTL1 acts as a microRNA (miRNA) sponge that actively regulates the expression of salt-inducible kinase 2 (SIK2) to sponge miR-526b and subsequently increases malignant phenotypes of cervical carcinomas cells. In a word, circAMOTL1 acts a carcinogenic role and miR-526b serves as the opposite function of antioncogene in the cervical carcinoma pathogenesis.ConclusionCircAMOTL1-miR-526b-SIK2 axis referred to the malignant progression and development of cervical carcinomas. CircAMOTL1 expression was inversely correlated with miR-526b and positively correlated with SIK2 mRNA in cervical cancer tissues. Thus, circAMOTL1 exerted an oncogenic role in cervical cancer progression through sponging miR-526b. Taken together, our study revealed that circAMOTL1 acted as an oncogene and probably was a potential therapeutic target for the cervical cancer.

With the discovery of new chemotherapeutic drugs, chemotherapy becomes increasingly valuable. However, the resistance of tumor cells to chemotherapeutic agents significantly limits the effectiveness and causes chemotherapy failure. MicroRNAs have been shown to regulate drug resistance in many types of cancer. In the present study, we measured the chemosensitivity of five bladder cancer (BCa) cell lines to seven commonly used chemotherapeutic drugs by Vita‑Blue assay. We then identified the most sensitive (5637) and most tolerant cell lines (H‑bc) and conducted a multi‑group test. This test included expression group analyses of coding and non‑coding genes (miR‑omic and RNA‑seq). Based on our analyses, we selected miR‑22‑3p as a target. We then determined its own target gene [neuroepithelial cell transforming 1 (NET1)] by bioinformatic analysis and confirmed this finding by TaqMan‑quantitative reverse transcription polymerase chain reaction (qRT‑PCR), western blot analysis and luciferase reporter assay. The effect of miR‑22‑3p on BCa multi‑chemoresistance was also determined by transfecting cells with the miR‑22‑3p‑mimic or miR‑22‑3p‑antagomiR. We assessed the involvement of NET1 in BCa chemoresistance by siRNA‑mediated NET1 inhibition or pINDUCER21‑enhanced green fluorescent protein‑NET1‑mediated overexpression. Plate colony formation and apoptosis assays were conducted to observe the effects of miR‑22‑3p and NET1 on BCa chemoresistance. In conclusion, our results suggest that miR‑22‑3p promotes BCa chemoresistance by targeting NET1 and may serve as a new prognostic biomarker for BCa patients.

Steroidogenic acute regulatory (StAR) protein is a rate-limiting protein, which is essential for transporting cholesterol into the mitochondria for steroidogenesis. StAR protein could be a marker for steroidogenic tissues. In this study, we investigated StAR protein levels in sex-cord stromal tumors (SCSTs) including 31 adult granulosa cell tumors, 3 juvenile granulosa cell tumors, 10 fibrothecomas, 2 luteinized thecomas, 4 Sertoli-Leydig cell tumors (SLCTs), 4 sclerosing stromal tumor and 3 Leydig cell tumors (LCTs), and 219 non-SCSTs. SCSTs were used for immunohistochemical staining of StAR protein, α-inhibin, calretinin, and CD99. All the 3 LCTs (100%) strongly stained for StAR protein; 30 of the 31 adult granulosa cell tumors (96%) showed focal staining of StAR protein; all the 10 fibrothecomas and 4 sclerosing stromal tumors (100%) were negative for StAR protein staining; StAR protein stained in Leydig cells but not in Sertoli cells in the 4 SLCTs. All the non-SCSTs were negative for StAR protein except for tumor cells in 4 adrenocortical adenomas and 2 adrenocortical carcinomas. Results of the study indicate that StAR protein is a useful marker for differential diagnosis of SCSTs. It is sensitive and specific for Leydig cells in tumors containing this component (LCT, SLCT), and can express focally in granulosa cell tumors. It is negative for Sertoli cells and nonluteinized theca cells.

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