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Abstract Background Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. Method CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C–C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. Conclusion ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

Abstract Papillary thyroid cancer (PTC) is a frequent thyroid malignancy. With the significant regulatory role in tumor progression, more attention has been employed to investigate mechanism of long noncoding RNAs (lncRNAs) in progression of PTC. We prospectively explored the mechanism whereby lncRNA SET‐binding factor 2‐antisense RNA1 (SBF2‐AS1) is implicated in pathogenesis of PTC. First, differentially expressed SBF2‐AS1 between PTC and normal adjacent thyroid tissues was determined, and result indicated a higher SBF2‐AS1 expression in PTC tissues than adjacent normal tissues. Moreover, highly SBF2‐AS1 expression predicted a poor prognosis in PTC patients. Second, SBF2‐AS1 overexpression promoted cell viability and cycle of PTC, while inhibited cell apoptosis. However, SBF2‐AS1 downregulation reduced viability and cycle, while promoted cell apoptosis. Moreover, SBF2‐AS1 could bind with miR‐431‐5p and showed negative correlation with miR‐431‐5p in PTC patients. Furthermore, miR‐431‐5p bind with cyclin‐dependent kinase (CDK) 14 and showed negative correlation with CDK14 in PTC patients. Finally, overexpression of CDK14 counteracted with the inhibitory role of SBF2‐AS1 downregulation on cell viability, cycle, and apoptosis of PTC. In conclusion, SBF2‐AS1 exhibited oncogenic property in PTC, and knockdown of SBF2‐AS1 could be a therapeutic strategy for PTC.