Sipi soup inhibits cancer‑associated fibroblast activation and the inflammatory process by downregulating long non‑coding RNA HIPK1‑AS

Abstract

Sipi soup (SPS), the aqueous extract derived from the root bark of Sophora japonical L, Salix babylonica L., Morus alba L., as well as Amygdalus davidiana (Carr.) C. de Vos, is a traditional Chinese medicine frequently used to prevent and treat infection and inflammation. However, the role of SPS in cancer-associated fibroblasts (CAFs) require further investigation. In the present study, the effects of SPS on fibroblast inactivation and the underlying mechanism were investigated. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression levels of fibroblast activation protein (FAP), interleukin (IL)-6, α-smooth muscle actin (α-SMA) and programmed cell death 4 (PDCD4). Flow cytometry was used to evaluate cell apoptosis. Immunofluorescence was used to determine the number of activated fibroblasts. The present study reported that SPS treatment did not affect the proliferative apoptotic potential of fibroblasts. Treatment with HeLa cell culture medium (CM) induced a significant increase in the expression levels of FAP, IL-6 and α-SMA, but reduced the expression of PDCD4. SPS reversed the effects of HeLa CM on the expression of these genes. Analysis with a long non-coding (lnc)RNA array of numerous differentially expressed lncRNAs revealed that the expression levels of the lncRNA homeodomain-interacting protein kinase 1 antisense RNA (HIPK1-AS) were increased in cervicitis tissues and cervical squamous cell carcinoma tissues compared with in normal cervical tissues. HIPK1-AS expression levels were upregulated in response to HeLa CM, but were decreased under SPS treatment. The downregulation of HIPK1-AS expression via short hairpin RNA abolished the effects of HeLa CM on the expression of inflammation-associated genes. The findings of the present study suggested that SPS may prevent the progression of cervical cancer by inhibiting the activation of CAF and the inflammatory process by reducing HIPK1-AS expression.

Fucoidan Inhibits the Progression of Hepatocellular Carcinoma via Causing lncRNA LINC00261 Overexpression

“…Compared with small molecule chemical drugs, natural products have higher therapeutic safety. They also could affect the expression level of lncRNAs, which is crucial for tumor progression (50)(51)(52)(53). In this research, we confirmed that fucoidan could effectively inhibit the progression of HCC.…”

“…lncRNAs were proved to be involved in a variety of biological activities, which is of great significance in regulating cell growth, differentiation and characteristics. They were also testified to play roles in the regulation of various types of tumors (50)(51)(52)(53). In this paper, we took advantage of High-Throughout sequencing to reveal the changes of lncRNA expression profiles in HCC after fucoidan treatment.…”

Immune-Related Four-lncRNA Signature for Patients with Cervical Cancer

“…HOTAIR was identified to promote the overactivation of the Wnt/ β -catenin signaling pathway by the downregulation of PCDH10, SOX17, AJAP1, and MAGI2 and also TET [ 42 ]. lncRNA HIPK1-AS has been proved to regulate the inflammatory process of cervical cancer [ 43 ]. Generally, there are still relatively few immune-related lncRNAs in CC.…”

Long Non-Coding RNAs as Regulators of Interactions between Cancer-Associated Fibroblasts and Cancer Cells in the Tumor Microenvironment

“…CAF-specific lncRNAs can be molecular targets of anticancer drugs. Sipi soup, a traditional Chinese medicine against infection and inflammation, prevents cancer cell-guided CAF activation and cancer progression in cervical cancer [ 65 ]. Through lncRNA microarray profiling, HIPK1 antisense RNA ( HIPK1-AS ) was shown to be induced in CAFs after treatment with conditioned medium from HeLa cells, and this was attenuated by Sipi soup.…”