Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung cancer

Zang, Farong; Rao, Yuanquan; Zhu, Xinhai; Wu, Zhibing; Jiang, Hao

doi:10.1186/s10020-020-00152-8

Cited by 26 publications

(22 citation statements)

References 39 publications

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“…In fact, several studies on NEAT1 lncRNA have shown that upregulated NEAT1 facilitated tumor cell viability, invasion, and migration in breast cancer 32 . In Non-small-cell lung carcinoma, Shikonin mediated NEAT1 suppression resulted in apoptotic cell death of paclitaxel-resistant cell lines 33 . In another study, lncRNA NEAT1 was shown to facilitate the progression of gallbladder cancer via the upregulation of Survivin expression, suggesting its potential use as a biomarker in gallbladder cancer 34 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

et al. 2021

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Cumulative evidence suggests added benefit for neoadjuvant chemotherapy (NAC) in a subset of triple-negative breast cancer (TNBC) patients. Herein we identified the long noncoding RNA (lncRNA) transcriptional landscape associated with TNBC resistance to NAC, employing 1758 single cells from three extinction and three persistence TNBC patients. Using Iterative Clustering and Guide-gene Selection (ICGS) and uniform manifold approximation and projection (UMAP) dimensionality reduction analysis, we observed single cells derived from each patient to largely cluster together. Comparing the lncRNA transcriptome from single cells through the course of NAC treatment revealed minimal overlap based on lncRNA transcriptome, suggesting substantial effects of NAC on lncRNA transcription. The differential analysis revealed upregulation of 202 and downregulation of 19 lncRNAs in the persistence group, including upregulation of five different transcripts encoding for the MALAT1 lncRNA. CRISPR/Cas9-mediated MALAT1 promoter deletion in BT-549 TNBC model enhanced sensitivity to paclitaxel and doxorubicin, suggesting a role for MALAT1 in conferring resistance. Mechanistically, whole transcriptome analysis of MALAT1-KO cells revealed multiple affected mechanistic networks as well as oxidative phosphorylation canonical and angiogenesis functional category. Interestingly, lncRNA profiling of MALAT1-depleted TNBC also revealed a number of altered lncRNAs in response to MALAT1 deletion, suggesting a reciprocal relationship between MALAT1 and a number of lncRNAs, including NEAT1, USP3-AS1, and LINC-PINT, in TNBC. Elevated expression of MALAT1, USP3-AS1, and LINC-PINT correlated with worse clinical outcomes in BC patients. Our data revealed the lncRNA transactional portrait and highlighted a complex regulatory network orchestrated by MALAT1 in the context of TNBC resistance to NAC therapy.

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Section: Discussionmentioning

confidence: 99%

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

et al. 2021

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“…Shikonin was demonstrated to suppress proliferation and induce cell cycle arrest in human colon cancer through inhibiting hypoxia-inducible factor-1 alpha signaling both in vitro and vivo 4 . Shikonin induced apoptosis of paclitaxel-resistant non-small cell lung cancer (NSCLC) cell lines and xenograft tumors through suppressing NEAT1 and Akt signaling 5 . Recently, Shikonin was reported to impede biosynthetic pathways critical for leukemia cell survival by the combination of dimethylaminoparthenolide 6 .…”

Section: Introductionmentioning

confidence: 99%

“…apoptosis of paclitaxel-resistant non-small cell lung cancer (NSCLC) cell lines and xenograft tumors through suppressing NEAT1 and Akt signaling 5 . Recently, Shikonin was reported to impede biosynthetic pathways critical for leukemia cell survival by the combination of dimethylaminoparthenolide 6 .…”

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confidence: 99%

Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model

Yang

Gao

et al. 2020

Sci Rep

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colorectal cancer (cRc) is a common malignancy occurring in the digestive system. Despite progress in surgery and therapy options, cRc is still a considerable cause of cancer mortality worldwide. in this study, a colon cancer patient-derived xenograft model was established to evaluate the antitumor activity of Shikonin. The protective effect underlying Shikonin was determined through assessing serum levels of liver enzymes (ALt, ASt) and kidney functions (Bun, Scr) in pDX mice. proteomics and metabolomics profiles were integrated to provide a systematic perspective in dynamic changes of proteins and global endogenous metabolites as well as their perturbed pathways. A total of 456 differently expressed proteins (DEPs), 32 differently expressed metabolites (DEMs) in tumor tissue, and 20 DEMs in mice serum were identified. The perturbation of arginine biosynthesis, purine metabolism, and biosynthesis of amino acids may mainly account for therapeutic mechanism of Shikonin. Furthermore, the expression of mRNAs participating in arginine biosynthesis (CPS1, OTC, Arg1) and do novo purine synthesis (GART, PAICS, ATIC) were validated through RT-qPCR. Our study provides new insights into the drug therapeutic strategies and a better understanding of antitumor mechanisms that might be valuable for further studies on Shikonin in the clinical treatment of colorectal cancer. Colorectal cancer (CRC), a digestive system tumor, is currently the third most common malignant cancer worldwide 1. Despite the improvements in diagnosis and therapeutic methods, the high risk of liver metastasis and poor prognosis of patients with advanced colorectal cancer remain to be addressed 2. Currently, surgery combined with chemotherapy and radiotherapy is still served as the predominant treatment for colorectal cancer. However, their side effects are considerable. Hence, the development of natural products has become a priority for the therapy of colorectal cancer. Shikonin (SHK), a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon (Sieb. et Zucc, Boraginaceae) (Fig. 1), has been reported to be highly effective against a variety of cancer types during the past decades 3. Shikonin was demonstrated to suppress proliferation and induce cell cycle arrest in human colon cancer through inhibiting hypoxia-inducible factor-1 alpha signaling both in vitro and vivo 4. Shikonin induced

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“…MALAT1 and NEAT1 have been widely studied non-coding RNAs, and some studies have demonstrated that they have clear correlations with various cancers such as hepatocellular carcinoma and lung cancer [ 30 – 33 ]. It has also been reported that MALAT1 can be used as ceRNA of miR-199a to promote the expression of ZHX1 , which in turn can regulate the proliferation of GBM cells [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of ceRNA network related to lincRNA in glioblastoma and prediction of clinical prognosis

Liu

Huang

et al. 2021

BMC Cancer

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Background Long intergenic non-coding RNAs (lincRNAs) are capable of regulating several tumours, while competitive endogenous RNA (ceRNA) networks are of great significance in revealing the biological mechanism of tumours. Here, we aimed to study the ceRNA network of lincRNA in glioblastoma (GBM). Methods We obtained GBM and normal brain tissue samples from TCGA, GTEx, and GEO databases, and performed weighted gene co-expression network analysis and differential expression analysis on all lincRNA and mRNA data. Subsequently, we predicted the interaction between lincRNAs, miRNAs, and target mRNAs. Univariate and multivariate Cox regression analyses were performed on the mRNAs using CGGA data, and a Cox proportional hazards regression model was constructed. The ceRNA network was further screened by the DEmiRNA and mRNA of Cox model. Results A prognostic prediction model was constructed for patients with GBM. We assembled a ceRNA network consisting of 18 lincRNAs, 6 miRNAs, and 8 mRNAs. Gene Set Enrichment Analysis was carried out on four lincRNAs with obvious differential expressions and relatively few studies in GBM. Conclusion We identified four lincRNAs that have research value for GBM and obtained the ceRNA network. Our research is expected to facilitate in-depth understanding and study of the molecular mechanism of GBM, and provide new insights into targeted therapy and prognosis of the tumour.

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Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung cancer

Cited by 26 publications

References 39 publications

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

Single-cell long noncoding RNA (lncRNA) transcriptome implicates MALAT1 in triple-negative breast cancer (TNBC) resistance to neoadjuvant chemotherapy

Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model

Comprehensive analysis of ceRNA network related to lincRNA in glioblastoma and prediction of clinical prognosis

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