Baofeng Yu

Ankyrin repeat domain 49 (ANKRD49) is highly expressed in non-small cell lung cancer (NSCLC) and promotes tumor cell invasion and metastasis by activating the p38/ATF-2/MMP or JNK/ATF-2/c-Jun/MMP pathways. Although epithelial-mesenchymal transition (EMT) is critical for tumor dissemination, the role of ANKRD49 in EMT remains unclear. This study aimed to investigate the effects of ANKRD49 on EMT in NSCLC and to elucidate its underlying molecular mechanisms. The expression levels of ANKRD49 and EMT markers were analyzed in lung adenocarcinoma (LUAD) tissues using tissue microarrays (TMAs) combined with immunohistochemistry (IHC). The role of ANKRD49 in EMT was assessed in vitro and in vivo through real-time qPCR, Western blot, and IHC. Key signaling molecules were quantified by real-time qPCR, Western blot, enzyme-linked immunosorbent assay (ELISA) and IHC. Transcriptional regulation of TGF-β1 by PKNOX1 was verified using luciferase reporter assays and chromatin immunoprecipitation (ChIP). Protein-protein interactions between ANKRD49 and PKNOX1 were examined by co-immunoprecipitation (Co-IP) and immunofluorescence microscopy. TMA analysis revealed a significant negative correlation between ANKRD49 and E-cadherin expression, whereas positive correlations were observed with α-smooth muscle actin (α-SMA) and TGF-β1. ANKRD49 overexpression promoted EMT, whereas its knockdown suppressed EMT in both cellular and animal models. Furthermore, ANKRD49 upregulation increased TGF-β1 levels, which are transcriptionally regulated by PKNOX1, while ANKRD49 silencing had the opposite effect. Mechanistically, ANKRD49 physically interacts with PKNOX1, and PKNOX1 binds to the TGF-β1 promoter, elevating TGF-β1 expression and subsequently activating SMAD signaling. Consistently, ANKRD49 and PKNOX1 levels were positively correlated in LUAD tissues. ANKRD49 facilitates EMT in NSCLC by interacting with PKNOX1 to activate the TGF-β1/SMAD pathway. PKNOX1 mediates this process through transcriptional regulation of TGF-β1. The online version contains supplementary material available at 10.1186/s12935-026-04240-3.

X-inactive specific transcript (Xist) is a main regulator of X chromosome inactivation in mammals, which silences most genes on X chromosome in a cis way. Xist is a kind of lncRNA, which cannot encode the transcript of protein. In addition, Xist RNA mediates the X chromosome inactivation (XCI) process to achieve dose compensation between the sexes. Recent studies have identified that Xist RNA regulates gene expression by recruiting factors/complexes to modify potential chromatin, which were involved in diseases such as neuroinflammation, autoimmune diseases and cancers. In this paper, the research progress of Xist RNA causing a series of diseases in mammalian cells is reviewed, which makes it a potential target for treating human diseases and provides a new direction for further study of diseases.

Background/Objectives: Long noncoding RNAs (lncRNAs) participate in the occurrence and development of non-small-cell lung carcinoma (NSCLC). But for certain lncRNAs, their effects on NSCLC remain unclear. This work discovered that lncRNA RP11-297P16.4 is elevated in NSCLC. Methods: LncRNA RP11-297P16.4 expression within LUAD tissues and cells was measured through RT-qPCR and Western blot. To assess the role of the lncRNA RP11-297P16.4 in NSCLC, gain- or loss-of-function experiments were conducted using an NSCLC mouse tumor model. Results: Silencing of the lncRNA RP11-297P16.4 inhibited the NSCLC cell line invasion and migration potential, but re-expression of the lncRNA RP11-297P16.4 had the opposite effect. A luciferase reporter confirmed that the lncRNA RP11-297P16.4 functions as a competitive endogenous RNA (ceRNA) through the sponge of miR-145-5p. The expression of lncRNA RP11-297P16.4 was negatively correlated to the level of miR-145-5p in NSCLC cells, which sponged miR-145-5p and suppressed tumor cell migration and invasion by targeting matrix metalloproteinase 2 (MMP-2) and MMP-9. Conclusions: Our findings suggested that the lncRNA RP11-297P16.4/miR-145-5p/MMP-2/9 regulatory axis is the key pathway for mediating the migration and invasion of NSCLC.

Background The satisfactory prognostic indicator of gastric cancer (GC) patients after surgery is still lacking. Perioperative plasma extracellular vesicular programmed cell death ligand-1 (ePD-L1) has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of postoperative plasma ePD-L1 has not been characterized. Methods We evaluated the prognostic value of preoperative, postoperative and change in plasma ePD-L1, as well as plasma soluble PD-L1, in short-term survival of GC patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyzes were used. And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and CA72-4) in prognostic of GC patients was made. Results The prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). The levels of postoperative ePD-L1 and ePD-L1 change are independent prognostic factors for overall survival and recurrence free survival of GC patients. High plasma level of postoperative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit. Conclusions The level of plasma postoperative ePD-L1 could be considered as a candidate prognostic biomarker of GC patients after resection.

Background: The satisfactory prognostic indicator of gastric cancer patients after surgery is still lacking. Peri-operative plasma extracellular vesicular (EV) PD-L1 has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of post-operative plasma EV PD-L1 has not been characterized. Methods: We evaluated the prognostic value of pre-operative, post-operative and change in plasma EV PD-L1, as well as plasma soluble PD-L1, in short-term survival of gastric cancer patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyses were used. Findings: The prognostic value of post-operative EV PD-L1 is superior to that of pre-operative EV PD-L1 on gastric cancer patients after resection. The levels of post-operative EV PD-L1 and EV PD-L1 change are independent prognostic factors for overall survival and recurrence free survival of gastric cancer patients. High plasma level of post-operative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit. Interpretation: The level of plasma post-operative EV PD-L1 could be considered as a prognostic biomarker of GC patients after resection. Funding Statement: This work was supported by following foundations: (a). National Natural Science Foundation of China (No. 30901821, 81172136, 82072737, 81201810). (b). Natural Science Foundation of Shanxi (No. 201701D121165, 201901D111190). (c). Research Project Supported by Shanxi Scholarship Council of China(No. 2020-194). (d). International Science and Technology Cooperation Project of Shanxi Provincial Key R&D Program (No. 201703D421023). (e). Shanxi Youth Science and Technology Research Fund (No. 201801D221069). (f). Open Fund from Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, China (No. KLMEC/SXMU202011). (g). Shanxi “1331 Project” Key Subjects Construction (No. 1331KSC). (h). Shanxi Province Science Foundation for Distinguished Young Scholar (No. 201901D211547). (i). Science and Research Fund of Shanxi Health Commission(No. 2019059). (j). the Doctor Project of Shanxi Cancer Hospital, China (No. 2017A06). (k). the Key Research Project of Shanxi Province, China (No. 201703D321010-1). (l). Natural Science Foundation of Guangdong Province, China (No. 2015A030313057). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All subjects had provided written informed consent. This study was approved by Shanxi Cancer Hospital Ethics Committee.

Ponatinib is a multi-target protein tyrosine kinase inhibitor, and its effects on hepatocellular carcinoma cells have not been previously explored. In the present study, we investigated its effects on hepatocellular carcinoma cell growth and the underlying mechanisms. Toward SK-Hep-1 and SNU-423 cells, ponatinib induces apoptosis by upregulation of cleaved caspase-3 and -7 and promotes cell cycle arrest in the G1 phase by inhibiting CDK4/6/CyclinD1 complex and phosphorylation of retinoblastoma protein. It inhibits the growth-stimulating mitogen-activated protein (MAP) kinase pathway, the phosphorylation of Src on both negative and positive regulation sites, and Jak2 and Stat3 phosphorylation. Surprisingly, it also activates the PDK1, the protein kinase B (Akt), and the mechanistic target of rapamycin (mTOR) signaling pathway. Blocking mTOR signaling strongly sensitizes cells to inhibition by ponatinib and makes ponatinib a much more potent inhibitor of hepatocellular carcinoma cell proliferation. These findings demonstrate that ponatinib exerts both positive and negative effects on hepatocellular cell proliferation, and eliminating its growth-stimulating effects by drug combination or potentially by chemical medication can significantly improve its efficacy as an anti-cancer drug.

A multifunctional targeted drug delivery platform (CDHA–MGO) has been successfully constructed by grafting β-cyclodextrin–hyaluronic acid polymers (CDHA) to Fe₃O₄–graphene oxide (MGO). The obtained CDHA–MGO nanocomposite has good water-dispersibility, easy magnetic separation, high near-infrared (NIR) photothermal heating, and excellent biocompatibility. The β-cyclodextrin-hyaluronic acid polymers efficaciously enhance the doxorubicin (DOX) loading amount up to 485.43 mg·g⁻¹. Meanwhile, the Fe₃O₄–graphene oxide provides a facile photothermal response mechanism to handle the NIR-triggered release of DOX in weak acidic solvent environments. Significantly, the DOX-loaded nanocomposite (DOX@CDHA–MGO) has displayed CD44 receptor-mediated active targeting recognition and chemo-photothermal synergistic therapy of hepatoma cells. These findings suggest that the as-prepared drug delivery platform would be of valuable potential for cancer-targeted photo-chemotherapy.

The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA‐seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles. Of 45 DEGs, Foxp2, Eomes, Hoxb3, Gpr56, Hap1, Nkx2‐1, Sez6l2, Wnt7b, Tbx20, Nfib, Cntn1 and Dcx had different isoforms, and the opposite expression pattern of different isoforms was observed for Gpr56, Nkx2‐1 and Sez6l2. In addition, alternative splicing, such as mutually exclusive exon, retained intron, skipped exon and alternative 3′ splice site was identified in 10 neural related differentially splicing genes, including Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan and App. Moreover, seven neural splicing factors, such as Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3 and Rbfox1 were differentially expressed during mouse neural tube development. Interestingly, nine DEGs identified above were dysregulated in retinoic acid‐induced NTDs model, indicating the possible important role of these genes in NTDs. Taken together, our study provides more comprehensive information on mouse neural tube development, which might provide new insights on NTDs occurrence. © 2017 IUBMB Life, 69(9):706–719, 2017