Phenanthroline-Decorated Covalent Organic Framework for Catalytic Synthesis of 2-Aminobenzothiazoles in Water.

2-Aminobenzothiazoles are widely used in the fields of pharmaceuticals and pesticides. Herein, we report a metal-free protocol for the preparation of 2-aminobenzothiazoles by a covalent organic framework (COF) catalyzed tandem reaction. In the presence of catalytic amount of phenanthroline-decorated COF (Phen-COF), a variety of 2-aminobenzothiazoles are obtained in excellent yields by the cross-coupling of 2-iodoanilines with isothiocyanates at room temperature in water. In addition, the COF-catalyst is very stable and can be reused at least seven times without loss of its catalytic activity.

Circular RNA Circ_0005962 Contributes to Lung Adenocarcinoma Cell Proliferation and Stem Cell Formation Through Sponging of miR-3611 and Modulating CYP24A1 Expression.

Recently, several studies have revealed that circular RNAs (circRNAs) play significant roles in various tumors, including lung adenocarcinoma (LUAD). Furthermore, it has been reported that circ_0005962 was upregulated in LUAD cells. Accordingly, this research is designed to investigate the mechanism of circ_0005962 on LUAD development. Circ_0005962, microRNA-3611 (miR-3611), and Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, cell cycle progression, and sphere formation ability were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, and sphere formation assay. Protein levels of proliferating cell nuclear antigen (PCNA), Ki67, NANOG, CD133, OCT4, and CYP24A1 were determined using Western blot assay. Using bioinformatics software (Starbase3.0 and TargetScan), the binding between miR-3611 and circ_0005962 or CYP24A1 was predicted and proved using RNA Immunoprecipitation (RIP) and RNA pull-down assays. A xenograft tumor model in vivo was used to analyze the biological role of circ_0005962 on LUAD cell growth. Increased circ_0005962 and CYP24A1, and reduced miR-3611 were observed in LUAD tissues and cell lines. Functional assays testified that circ_0005962 depletion might hinder LUAD cell proliferation and sphere formation capability, but induced cell apoptosis in vitro. Molecular mechanism experiments exhibited that circ_0005962 served as a miR-3611 sponge and mediated CYP24A1 content by absorbing miR-3611. Additionally, silencing of circ_0005962 inhibited tumor growth in xenograft modes. Together, circ_0005962 was overexpressed in LUAD, and its deficiency repressed LUAD progression via targeting the miR-3611/ CYP24A1 axis, providing a novel mechanism for understanding the development of LUAD.

Long non-coding RNA OGFRP1 regulates cell proliferation and ferroptosis by miR-299-3p/SLC38A1 axis in lung cancer.

Lung cancer is devastating cancer that ranks as the leading cause of cancer-related death. Long noncoding RNA (lncRNA) opioid growth factor receptor pseudogene 1 (OGFRP1) was recognized as an oncogene in many cancers. However, the molecular mechanism of OGFRP1 in lung cancer is still poorly understood. The expression of target RNAs and genes was detected by quantitative real-time PCR and western blot. The interaction between miR-299-3p and OGFRP1 or solute carrier family 38 member 1 (SLC38A1) was predicted by StarbaseV3.0 and verified by dual-luciferase reporter assay and Pearson's correlation coefficient. Besides, a transplantation model of human lung cancer in nude mice was established to evaluate the role of OGFRP1 in lung cancer. OGFRP1 and SLC38A1 were overexpressed, whereas miR-299-3p was lowly expressed in lung cancer tumors and cells. OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. Besides, Furthermore, miR-299-3p inhibitor or SLC38A1 overexpression attenuated OGFRP1 depletion-induced suppression on cell proliferation and ferroptosis in lung cancer. Animal experiments indicated that OGFRP1 deficiency restrained tumor growth in vivo by regulating the miR-299-3p/SLC38A1 axis. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer.

Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis.

BACKGROUND: Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. METHODS: The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. RESULTS: We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. CONCLUSION: Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

Circ_0007031 Silencing Inhibits Cell Proliferation and Induces Cell Apoptosis via Downregulating MELK at a miR-485-3p-Dependent Way in Colorectal Cancer.

Colorectal cancer (CRC) is a malignant cancer with an increasing incidence. Circular RNA (circRNA) is recently found to participate in the regulation of CRC progression. However, the role of circ_0007031 in CRC malignant progression remains elusive. 50 CRC patients were implicated in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the RNA expression of circ_0007031, microRNA-485-3p (miR-485-3p) and maternal embryonic leucine zipper kinase (MELK). Western blot analysis was conducted to determine protein expression. Cell viability and proliferation were demonstrated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine (EdU) assays, respectively. Cell cycle and apoptosis were investigated by flow cytometry analysis. The interaction among circ_0007031, miR-485-3p and MELK was predicted by online databases, and identified by dual-luciferase reporter assay. Mouse model assay was conducted to reveal the effect of circ_0007031 on tumor formation in vivo. Circ_0007031 and MELK expression were obviously increased, while miR-485-3p expression was decreased in CRC tissues and cells compared with normal colorectal tissues or cells. Circ_0007031 knockdown repressed proliferation, whereas induced cell arrest at G0/G1 phase and apoptosis. On the opposite, circ_0007031 overexpression promoted cell proliferation and induced cell arrest at S phase. Additionally, miR-485-3p inhibitors attenuated circ_0007031 silencing-mediated CRC cell malignancy. MiR-485-3p was unveiled to regulate CRC cell processes via targeting MELK. Circ_0007031 controlled MELK expression via interacting with miR-485-3p. Furthermore, circ_0007031 contributed to tumor formation in vivo. Circ_0007031 knockdown repressed CRC malignant progression by reducing MELK expression through associating with miR-485-3p, suggesting that circ_0007031 was a potential target for the therapy of CRC.

Metalloporphyrin and Ionic Liquid-Functionalized Covalent Organic Frameworks for Catalytic CO2 Cycloaddition via Visible-Light-Induced Photothermal Conversion.

We report the construction of a porphyrin and imidazolium-ionic liquid (IL)-decorated and quinoline-linked covalent organic framework (COF, abbreviated as COF-P1-1) via a three-component one-pot Povarov reaction. After post-synthetic metallization of COF-P1-1 with Co(II) ions, the metallized COF-PI-2 is generated. COF-PI-2 is chemically stable and displays highly selective CO2 adsorption and good visible-light-induced photothermal conversion ability (ΔT = 26 °C). Furthermore, the coexistence of Co(II)-porphyrin and imidazolium-IL within COF-PI-2 has guaranteed its highly efficient activity for CO2 cycloaddition. Of note, the needed thermal energy for the reactions is derived from the photothermal conversion of the Co(II)-porphyrin COF upon visible-light irradiation. More importantly, the CO2 cycloaddition herein is a "window ledge" reaction, and it can proceed smoothly upon natural sunlight irradiation. In addition, a scaled-up CO2 cycloaddition can be readily achieved using a COF-PI-2@chitosan aerogel-based fixed-bed model reactor. Our research provides a new avenue for COF-based greenhouse gas disposal in an eco-friendly and energy- and source-saving way.

Long Noncoding RNA SNHG7 Accelerates Proliferation, Migration and Invasion of Non-Small Cell Lung Cancer Cells by Suppressing miR-181a-5p Through AKT/mTOR Signaling Pathway.

PURPOSE: Non-small cell lung cancer (NSCLC) is a typical epithelial lung cancer with high metastasis, incidence and mortality. In recent years, long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) has been identified as significant regulator in different cancer types, including NSCLC. However, the underlying molecular mechanism of SNHG7 during NSCLC tumorigenesis and progression remains largely unclear. METHODS: SNHG7 and miR-181a-5p expression in NSCLC tumors and cells were detected by qRT-PCR. Cell viability, migration, invasion and apoptosis were evaluated by CCK-8, transwell and flow cytometry assay, respectively. A549 and NCI-H1299 xenograft mice model was constructed by subcutaneously injecting cells stably transfected with sh-SNHG7 and sh-NC. The interaction between SNHG7 and miR-181a-5p was validated by luciferase reporter system, RIP and RNA pull down assay. Protein expression of cleaved caspase 3, proliferating cell nuclear antigen (PCNA), AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR was analyzed by Western blot. RESULTS: SNHG7 expression was up-regulated while miR-181a-5p expression was down-regulated in NSCLC tumors, especially those from patients at Phase III+IV, compared with normal tissues. However, SNHG7 depletion attenuated tumor growth in vitro and in vivo. Moreover, miR-181a-5p inhibitor abolished SNHG7 silencing induced inhibition on proliferation, migration and invasion in NSCLC. Subsequently, we found SNHG7 modulated cell progression by targeting miR-181a-5p and activating AKT/mTOR signaling pathway. CONCLUSION: SNHG7 accelerates proliferation, migration and invasion of NSCLC by suppressing miR-181a-5p through AKT/mTOR signaling pathway, thus presenting desirable biomarkers for NSCLC therapy.

[Antitumor effect of capsaicin on colorectal carcinoma xenograft in nude mice].

OBJECTIVE: To evaluate the effect of capsaicin on nude mice xenografted with colorectal carcinoma cells, and to explore its mechanism of action. METHODS: A nude mouse model of colorectal cancer was established by subcutaneous inoculation of human colorectal carcinoma HT-29 cells. Terminal deoxynucleotidyl transferase-mediated nicked labeling assay (TUNEL) was undertaken to detect the cell proliferation and apoptosis in the xenograft tissue in nude mice. Immunohistochemical (IHC) staining and Western blot were used to detect the expression of HSP27, Cyt-C and active caspase-3. RESULTS: The tumor growth of the groups C10 and C20 was significantly slower than that of the group NS. The integrated optical density (IOD) of both the group C5 (2532.14 ± 578.11) and group C10 (6364.03 ± 1137.98) was significantly higher than that of the group NS (760.12 ± 238.05), (P < 0.05). The integrated optical density (IOD) of the group C20 was (15743.96 ± 1855.95), significantly higher than that of the groups C10, C5 and NS (all were P < 0.01). Immunohistochemistry showed that the cytoplasmic expression of HSP27 was strongly positive in the group NS, and significantly reduced with the increasing dose of capsaicin in the treated groups. The expression of active caspase-3 and Cyt-C in the group NS was weakly positive, and was significantly increased with the increasing dose of capsaicin in the groups C5 and C10 (P < 0.05), and the expression of active caspase-3 and Cyt-C of the group C20 was significantly higher than that of the groups C5, C10 and NS (P < 0.01). Western blot analysis showed that both the expressions of HSP27 of the group C5 (0.73 ± 0.05) and the group C10 (0.41 ± 0.03) were significantly lower than that of the group NS (P < 0.05). The expression of HSP27 of the group C20 (0.22 ± 0.06) was significantly lower than that of the groups C5, C10 and NS (P < 0.01). The expressions of active-caspase-3 and Cyt-C in the group C5 were (2.57 ± 0.34) and (2.03 ± 0.38), significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C10 were (4.23 ± 0.45) and (3.13 ± 0.44), also significantly higher than those of the group NS (P < 0.05). The expressions of active-caspase-3 and Cyt-C in the group C20 were (5.78 ± 0.48) and (4.92 ± 0.52), significantly higher than those of the group C5, C10 and NS (P < 0.01). TUNEL analysis showed that there was a significant difference of cell apoptosis in comparison of each two groups. The higher dose of capsaicin was used, the more apoptosis was observed. CONCLUSIONS: Capsaicin can significantly inhibit the tumor growth and induce cell apoptosis in the colorectal carcinoma xenograft in nude mice. Its mechanism of action is possibly related with the down-regulation of HSP27 expression and up-regulation of expression of active caspase-3 and Cyt-C in the colorectal carcinoma xenograft in nude mice.