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Background: Solute carrier family 34 member 2 (SLC34A2) has been implicated in the development of various malignancies. However, the clinical significance and underlying molecular mechanisms of SLC34A2 in esophageal squamous cell carcinoma (ESCC) remain elusive. Methods: Western blotting, quantitative real‐time PCR and immunohistochemistry were utilized to evaluate the expression levels of SLC34A2 mRNA/protein in ESCC cell lines or tissues. Kaplan–Meier curves were employed for survival analysis. CCK‐8, colony formation, EdU and xenograft tumor model assays were conducted to determine the impact of SLC34A2 on ESCC cell proliferation. Cell cycle was examined using flow cytometry. RNA‐sequencing and enrichment analysis were carried out to explore the potential signaling pathways. The autophagic flux was evaluated by western blotting, mRFP‐GFP‐LC3 reporter system and transmission electron microscopy. Immunoprecipitation and mass spectrometry were utilized for identification of potential SLC34A2‐interacting proteins. Cycloheximide (CHX) chase and ubiquitination assays were conducted to test the protein stability. Results: The expression of SLC34A2 was significantly upregulated in ESCC and correlated with unfavorable clinicopathologic characteristics particularly the Ki‐67 labeling index and poor prognosis of ESCC patients. Overexpression of SLC34A2 promoted ESCC cell proliferation, while silencing SLC34A2 had the opposite effect. Moreover, SLC34A2 induced autophagy to promote ESCC cell proliferation, whereas inhibition of autophagy suppressed the proliferation of ESCC cells. Further studies showed that SLC34A2 interacted with an autophagy‐related protein STX17 to promote autophagy and proliferation of ESCC cells by inhibiting the ubiquitination and degradation of STX17. Conclusions: These findings indicate that SLC34A2 may serve as a prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer‐related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome‐mediated degradation, which further mediates the activation of the AKT/GSK3β/epithelial‐to‐mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin‐3‐gallate‐lysozyme (EGCG‐LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG‐LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG‐LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post‐transcriptional gene silencing. In addition, EGCG‐LYS carrying si‐circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG‐LYS fibrils delivery system provides a new tool and approach for the treatment of GC. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the leading causes of therapeutic failure in gastric cancer (GC) treatment. Recent studies have shown lncRNAs play pivotal roles in regulating GC chemoresistance. Nanocarriers delivery of small interfering RNAs (siRNAs) to silence cancer‐related genes has become a novel approach to cancer treatment research. However, finding target genes and developing nanosystems capable of selectively delivering siRNAs for disease treatment remains a challenge. In this study, a novel lncRNA TMEM44‐AS1 that is related to 5‐FU resistance is identified. TMEM44‐AS1 has the ability to bind to and sponge miR‐2355‐5p, resulting in the upregulated PPP1R13L expression and P53 pathway inhibition. Next, a new nanocarrier called chitosan‐gelatin‐EGCG (CGE) is developed, which has a higher gene silencing efficiency than lipo2000, to aid in the delivery of a si‐TMEM44‐AS1 can efficiently silence TMEM44‐AS1 expression to synergistically reverse 5‐FU resistance in GC, leading to a markedly enhanced 5‐FU therapeutic effect in a xenograft mouse model of GC. These findings indicate that TMEM44‐AS1 may estimate 5‐FU therapy outcome among GC cases, and that systemic si‐TMEM44‐AS1 delivery combined with 5‐FU therapy is significant in the treatment of patients with recurrent GC. [ABSTRACT FROM AUTHOR]