Long noncoding RNA (lncRNA) metallothionein 1 J, pseudogene (MT1JP) is downregulated in triple-negative breast cancer and upregulates microRNA-138 (miR-138) to downregulate hypoxia-inducible factor-1α (HIF-1α).

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study explored the molecular mechanism and influences of metallothionein 1 J, pseudogene (MT1JP), microRNA-138 (miR-138), and hypoxia-inducible factor-1α (HIF-1α) on TNBC cell proliferation and migration. We confirmed TNBC cases by immunohistochemistry (IHC) staining. The expression of MT1JP in two types of tissue collected from 78 TNBC patients was detected by performing real-time quantitative fluorescence PCR (RT-qPCR). To further evaluate the relationship among MT1JP, miR-138 and HIF-1α, expression vectors of MT1JP and HIF-1α, as well as miR-138 mimic and inhibitor, were delivered into BT-549 cells. We observed that MT1JP was downregulated in TNBC. MT1JP was positively correlated with miR-138 but negatively correlated with HIF-1α in TNBC tissues. In TNBC cells, upregulation of miR-138 and downregulation of HIF-1α were observed after overexpression of MT1JP. In addition, overexpression of miR-138 resulted in downregulation of HIF-1α but did not affect the expression of MT1JP. Decreased proliferation rate of TNBC cells was observed after overexpression of MT1JP and miR-138. HIF-1α increased cell proliferation and migration. HIF-1α also suppressed the role of MT1JP and miR-138 in TNBC cell proliferation and migration. In conclusion, our findings demonstrated that MT1JP inhibited TNBC by regulating the miR-138/HIF-1α axis, indicating that MT1JP might serve as a biomarker or target for TNBC treatment.

Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides.

Since the seminal work of Zhang in 2016, donor-acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from -1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•-*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ -1.9 to -2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C-B, C-P, and C-C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.

Chemo- and Diastereoselective Synthesis of Pyrrolidines from Aroylformates and δ-Tosylamino Enones via P(NMe2)3-Mediated Reductive Amination/Base-Catalyzed Michael Addition Cascade.

A novel P(NMe2)3-mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones has been developed that affords a facile synthesis of functionalized pyrrolidines in moderate to excellent yields with exclusive chemoselectivity and high diastereoselectivity. Mechanistic investigation reveals that the reaction proceeds through an unprecedented P(NMe2)3-mediated reductive amination/base-catalyzed Michael addition cascade. The reaction herein also represents the first study of the reactivity patterns of the Kukhtin-Ramirez adducts toward ambiphilic nucleophile-electrophiles.

Condensation of 1,2-dicarbonyl compounds with modified Huisgen zwitterions: synthesis of N-aryl-N-acyl hydrazones.

A phosphine-mediated deoxygenative condensation of 1,2-dicarbonyl compounds such as aroylformates, α-diketones, and isatins with arylazocarboxylates has been developed for a facile synthesis of N-aryl-N-acyl hydrazones in moderate to excellent yields under very mild conditions. Mechanistic investigation based on 31P NMR tracking experiments unveils that the reaction is initiated with the in situ formation of the modified Huisgen zwitterions from arylazocarboxylates and PPh3 and proceeds via a nitrogen to nitrogen ester group migration process. This study also represents the first exploration of the reactivity patterns of the modified Huisgen zwitterions derived from arylazocarboxylates toward electrophiles such as 1,2-dicarbonyl compounds.

Loss of miR-873 contributes to gemcitabine resistance in triple-negative breast cancer via targeting ZEB1.

Gemcitabine-based chemotherapy is commonly applied for the treatment of breast cancer in a clinical setting. However, acquired resistance to chemotherapy primarily results in treatment failure and eventually culminates in patient mortality. Aberrant expression of microRNAs (miRNAs) has been demonstrated to be implicated in the development of chemoresistance; however, the role of miR-873 in the chemoresistance of breast cancer and its underlying mechanism have not been completely elucidated. Herein, using cell viability assays, the present study demonstrated that overexpression of miR-873 sensitized triple-negative breast cancer (TNBC) cells (MDA-MB-231 and BT549) towards gemcitabine treatment, while inhibition of miR-873 promoted resistance of TNBC cells to gemcitabine exposure. The 3' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) was predicted as a candidate target of miR-873, and the regulatory association between ZEB1 and miR-873 was validated with a dual luciferase assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis confirmed that miR-873 mimics reduced ZEB1 at mRNA and protein levels in MDA-MB-231 and BT549 cells. As ZEB1 was previously reported to interact with Yes associated protein (YAP) to promote cancer progression. The present study observed that miR-873 overexpression decreased the expression of YAP target genes AXL receptor tyrosine kinase, connective tissue growth factor and cysteine rich angiogenic inducer 61 at mRNA and protein levels. Additionally, elevation of the ZEB1 level and reduction of the miR-873 level were detected in gemcitabine-resistant MDA-MB-231 (MDA-MB-231GEMr) cells, which were accompanied with stronger proliferative ability, compared with parental cells. Overexpression of miR-873 or ZEB1 knockdown reversed chemoresistance of MDA-MB-231GEMr cells by inducing a notable cell growth arrest upon gemcitabine exposure. In conclusion, the data obtained by the present study demonstrated that the decrease of miR-873 promoted the development of gemcitabine resistance in TNBC via elevation of ZEB1 expression, which indicated that miR-873 may be a promising predictor for gemcitabine sensitivity in patients with TNBC.

Short-term effects of splenectomy on serum fibrosis indexes in liver cirrhosis patients.

OBJECTIVE: To determine the changing patterns of 4 liver fibrosis markers pre and post splenectomy (combined with pericardial devascularization [PCDV]) and to examine the short-term effects of splenectomy on liver fibrosis. METHODS: Four liver fibrosis markers of 39 liver cirrhosis patients were examined pre, immediately post, 2 days post, and 1 week post (15 cases) splenectomy (combined with PCDV). RESULTS: The laminin (LN) level decreased immediately post surgery compared with the preoperative LN level (P < 0.05). The type IV collagen level decreased immediately post surgery compared with that pre surgery (P < 0.05), it significantly increased (P < 0.05) 2 days post surgery and significantly decreased 1 week post surgery (P < 0.05). Hyaluronic acid and the procollagen III N-terminal peptide levels increased significantly 2 days post surgery compared with that pre and immediately post surgery, they significantly decreased 1 week post surgery compared to 2 days post surgery (P < 0.05). CONCLUSIONS: In the short-term, the 4 liver fibrosis markers and the FibroScans post splenectomy showed characteristic changes, splenectomy may transiently initiate the degradation process of liver fibrosis.