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Biomedical subjects

Jianwei Sun

Publications and source records attributed to Jianwei Sun.

9 recordsLinked to original sources

Exon 21 skipping in ARHGAP10: A splicing switch that governs breast cancer metastasis.

Rho GTPase-activating protein 10 (ARHGAP10) is recognized as a tumor suppressor, yet the functional impact of its alternative splicing isoforms on breast cancer metastasis remains unclear. This study aimed to elucidate the role and regulatory mechanism of ARHGAP10 exon 21 skipping in breast cancer progression. Our research results indicate that in metastatic breast cancer cells, the full-length isoform ARHGAP10-L is downregulated, whereas the truncated ARHGAP10-S is upregulated. The RNA-binding protein HNRNPA0 directly binds to intron 21 of ARHGAP10 pre-mRNA, promoting exon-21 skipping and ARHGAP10-S production. Functionally, ARHGAP10-L and ARHGAP10-S exert opposing effects on breast cancer cell malignancy: ARHGAP10-L suppresses migration, invasion, and lung metastasis, whereas ARHGAP10-S promotes these aggressive phenotypes. Moreover, ARHGAP10-S exhibits enhanced binding to CDC42 and is associated with increased AKT phosphorylation. In a nude mouse model, HNRNPA0 drove lung metastasis by upregulating ARHGAP10-S. These findings establish the HNRNPA0-ARHGAP10 splicing axis as a key regulator of breast cancer metastasis, in which ARHGAP10-S promotes progression via the AKT pathway whereas ARHGAP10-L acts as a tumor suppressor, highlighting the therapeutic potential of targeting this splicing event to combat metastasis.

ARHGAP10 (RhoGTPase activating protein 10)↗

Solution-liquid-solid growth of semiconductor nanowires.

The serendipitously discovered solution-liquid-solid (SLS) mechanism has been refined into a nearly general synthetic method for semiconductor nanowires. Purposeful control of diameters and diameter distributions is achieved. The synthesis proceeds by a solution-based catalyzed-growth mechanism in which nanometer-scale metallic droplets catalyze the decomposition of metallo-organic precursors and crystalline nanowire growth. Related growth methods proceeding by the analogous vapor-liquid-solid (VLS) and supercritical fluid-liquid-solid (SFLS) mechanisms are known, and the relative attributes of the methods are compared. In short, the VLS method is most general and appears to afford nanowires of the best crystalline quality. The SLS method appears to be advantageous for producing the smallest nanowire diameters and for variation and control of surface ligation. The SFLS method may represent an ideal compromise. Recent results for SLS growth are summarized.

Journal Article↗

Au- and pt-catalyzed cycloisomerizations of 1,5-enynes to cyclohexadienes with a broad alkyne scope.

We describe the development of gold- and platinum-catalyzed cycloisomerizations of 1,5-enynes. This catalytic process displays a wide alkyne scope and furnishes a range of highly functionalized 1,4- and 1,3-cyclohexadienes. In the case of 1-siloxy-1-yne-5-enes, the reactions are efficiently catalyzed by AuCl (1 mol %) at ambient temperature to afford siloxy cyclohexadienes or the corresponding 1,2- and 1,3-cyclohexenones upon subsequent protodesilylation. We propose that the reaction proceeds via a novel mechanism involving a series of 1,2-alkyl shifts. Elucidation of this unusual reaction mechanism enabled us, in turn, to significantly expand the scope of the cycloisomerization by incorporation of a quaternary center at the C(3) position of the enyne. Indeed, we established that PtCl(2) (5 mol %) efficiently catalyzed the cycloisomerizations of 1,5-enynes containing terminal, internal, and arene-conjugated alkynes. Since a variety of 1,5-enynes are readily accessible, the cycloisomerization provides a rapid approach to a wide range of highy substituted cyclohexadienes for many subsequent synthetic applications.

Journal Article↗

Brønsted acid-promoted cyclizations of 1-siloxy-1,5-diynes.

We have developed the first HNTf2-promoted 5-endo-dig cyclizations of 1-siloxy-1,5-diynes, which proceed with concomitant formation of C-Hal bonds as a result of halide abstraction from a halocarbon by the intermediate alkenyl cation. This process is enabled by a chemoselective activation of the more electron-rich siloxy alkyne moiety of the diyne cyclization precursor and represents an efficient and highly diastereoselective method for assembly of a range of beta-halo enones.

Journal Article↗

Nonracemic Betti base as a new chiral auxiliary: application to total syntheses of enantiopure (2S,6R)-dihydropinidine and (2S,6R)-isosolenopsins.

Total syntheses of enantiopure alkaloidal natural products (2S,6R)-dihydropinidine (as hydrochloride) and (2S,6R)-isosolenopsins (as hydrochlorides) were achieved in four steps and in 80-82% total yields by using a synthetic strategy of the formation-cleavage of 1,3-oxazinane. (S)-Betti base was proved to be an excellent chiral auxiliary and a novel Pd/C catalyzed N-debenzylation straightforward to amine hydrochloride was developed in the presence of CH2Cl2.

Alkaloids↗

Preparation of 2-pyridone-containing tricyclic alkaloid derivatives as potential inhibitors of tumor cell proliferation by regioselective intramolecular N- and C-acylation of 2-pyridone.

A novel and practical preparation of 2-pyridone-containing tricyclic alkaloid derivatives was developed. By regioselective intramolecular N- and C-acylation of 2-(4-aryl-2-pyridon-6-yl)benzoic acid, a pair of structural isomers 2-aryl pyrido[2,1-a]isoindole-4,6-diones and 4-aryl 1-methyl-1H-indeno[1,2-b]-pyridine-2,5-diones, as potential inhibitors of tumor cell proliferation, were prepared respectively.

Acylation↗

Highly efficient chemoselective deprotection of O,O-acetals and O,O-ketals catalyzed by molecular iodine in acetone.

An extremely convenient method for deprotection of acetals and ketals catalyzed by molecular iodine (10 mol %) in acetone is reported. The protocol achieved the deprotection of acyclic or cyclic O,O-acetals and O,O-ketals in excellent yields within a few minutes under neutral conditions. The double bond, hydroxyl group, and acetate group remained unchanged, and the highly acid-sensitive furyl, tert-butyl ethers, and ketone-oxime stayed intact under these conditions.

Acetals↗