Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, the physiological functions of only a few OR types have been elucidated in skin cells. All-trans retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR α or RAR γ antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca2+ entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR α- and γ-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.
Objective: This study aimed to identify proteins related to paclitaxel and carboplatin chemoresistance in cervical cancer. Methods: Quantitative proteomic analysis was performed on normal SiHa cells and those treated with paclitaxel and carboplatin for 14 days, with isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify related processes and differentially expressed proteins. Results: A total of 67 and 96 differentially expressed proteins were identified in the paclitaxel-and carboplatin-treated groups, respectively. GO and KEGG enrichment analyses identified 53 (43 upregulated and 10 downregulated) and 85 differentially expressed proteins (70 upregulated and 15 downregulated) in the paclitaxel-and carboplatin-treated groups, respectively. The cell counting kit-8 results revealed that APOA1 was overexpressed in both the paclitaxel-and carboplatin-resistant SiHa cells compared with the control cells. Immunohistochemistry showed that APOA1 was highly expressed in the paclitaxel-and carboplatin-resistant squamous cell carcinoma of the cervix. Conclusion: This study is the first to use iTRAQ to identify paclitaxel-and carboplatinresistance proteins in cervical cells. We identified several proteins previously unassociated with paclitaxel and carboplatin resistance in cervical cancer, thereby expanding our understanding of paclitaxel and carboplatin resistance mechanisms. Moreover, these findings indicate that the APOA1 protein could serve as a potential marker for monitoring and predicting paclitaxel and carboplatin resistance levels.
We present a molecular beacon‐based electrochemical biosensor with high sensitivity and specificity for the detection of microRNA‐21. A special oligonucleotide probe was prepared containing a nucleotide sequence complementary to miR‐21 and consecutively linking eight and six thymines to the 3′ and 5′ ends, respectively, to allow the formation of a T‐Hg2+‐T complex‐based molecular beacon on the electrode surface by the selective binding of Hg2+ ions. The introduction of multiple thymines at the end of the probe avoids base overlapping between the miRNA sequence and the molecular beacon formation sequence, enabling a universal probe design that can detect all types of miRNAs. A ferrocene moiety was attached to the 5′‐end of the specially designed probe as an electrochemical signal indicator. The molecular beacons are formed by six consecutive T‐Hg2+‐T pairs by Hg2+ addition, and the molecular beacons are destroyed by perfect hybridization between 22 bases as a result of miR‐21 addition. Based on this detection mechanism, we were able to detect miR‐21 with LODs of 0.64 pM and 1.08 pM in buffer solution and human serum, respectively. In addition, the specifically designed oligonucleotide probe showed perfect specificity in detecting only miR‐21 without binding to other miRNAs. Finally, the sensor showed excellent miR‐21 recovery ability from samples spiked into serum, indicating that the method described in this study worked perfectly, even in a turbid complex matrix such as human serum.
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