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      Solamargine inhibits the growth of hepatocellular carcinoma and enhances the anticancer effect of sorafenib by regulating HOTTIP‐TUG1/miR‐4726‐5p/MUC1 pathway

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          Abstract

          Hepatocellular carcinoma (HCC) is one of the most common primary malignancies. Drug resistance has significantly prevented the clinical application of sorafenib (SF), a first‐line targeted medicine for the treatment of HCC. Solamargine (SM), a natural alkaloid, has shown potential antitumor activity, but studies about antitumor effect of SM are obviously insufficient in HCC. In the present study, we found that SM significantly inhibited the growth of HCC and enhanced the anticancer effect of SF. In brief, SM significantly inhibited the growth of HepG2 and Huh‐7 cells. The combination of SM and SF showed a synergistic antitumor effect. Mechanistically, SM downregulated the expression of long noncoding RNA HOTTIP and TUG1, followed by increasing the expression of miR‐4726‐5p. Moreover, miR‐4726‐5p directly bound to the 3′‐UTR region of MUC1 and decreased the expression of MUC1 protein. Overexpression of MUC1 partially reversed the inhibitory effect of SM on HepG2 and Huh‐7 cells viability, which suggested that MUC1 may be the key target in SM‐induced growth inhibition of HCC. More importantly, the combination of SM and SF synergistically restrained the expression of MUC1 protein. Taken together, our study revealed that SM inhibited the growth of HCC and enhanced the anticancer effect of SF through HOTTIP‐TUG1/miR‐4726‐5p/MUC1 signaling pathway. These findings will provide potential therapeutic targets and strategies for the treatment of HCC.

          Abstract

          In vitro and in vivo results showed that solamargine (SM) significantly inhibited the growth and enhanced the antitumor effect of sorafenib by regulating the HOTTIP‐TUG1/miR‐4726‐5p/MUC1 signaling pathway in hepatocellular carcinoma (HCC). In brief, SM significantly downregulated the expression of long noncoding RNA HOTTIP and TUG1. Overexpression of HOTTIP and TUG1 decreased miR‐4726‐5p and reversed the effect of SM‐increased expression of miR‐4726‐5p through acting the sponges of miR‐4726‐5p. Moreover, miR‐4726‐5p directly bound to the 3′‐UTR region of MUC1, followed by reducing the expression of MUC1 protein. On the other hand, SM drastically decreased the promoter activity and protein expression of MUC1, overexpression of MUC1 significantly reversed the inhibitory effect of SM on HCC cells. More importantly, the combination of SM and sorafenib have a remarkable synergy on the downregulation of MUC1 and growth inhibition of HCC. Therefore, MUC1 may be the criticaltarget in the SM‐induced growth inhibition and the anticancer synergy effect of SM and sorafenib in HCC.

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          Long Noncoding RNA (lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer

          Colorectal cancer (CRC) is the third most common cancer and has a high metastasis and reoccurrence rate. Long noncoding RNAs (lncRNAs) play an important role in CRC growth and metastasis. Recent studies revealed that lncRNAs participate in CRC progression by coordinating with microRNAs (miRNAs) and protein-coding mRNAs. LncRNAs function as competitive endogenous RNAs (ceRNAs) by competitively occupying the shared binding sequences of miRNAs, thus sequestering the miRNAs and changing the expression of their downstream target genes. Such ceRNA networks formed by lncRNA/miRNA/mRNA interactions have been found in a broad spectrum of biological processes in CRC, including liver metastasis, epithelial to mesenchymal transition (EMT), inflammation formation, and chemo-/radioresistance. In this review, we summarize typical paradigms of lncRNA-associated ceRNA networks, which are involved in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the competitive crosstalk among RNA transcripts and the novel targets for CRC prognosis and therapy.
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            Goals and targets for personalized therapy for HCC

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              MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance

              Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene expression via post-transcriptional regulation of mRNA. Nevertheless, few studies have conceded the role of miRNAs in activation of gene expression. A large body of data generated by numerous studies is suggestive of their tumor-suppressing, oncogenic, diagnostic and prognostic biomarker roles in lung cancer. They have also been implicated in regulating cancer cell metabolism and resistance or sensitivity towards chemotherapy and radiotherapy. Further, miRNAs have also been convoluted in regulation of immune checkpoints - Programmed death 1 (PD-1) and its ligand (PD-L1). These molecules play a significant role in tumor immune escape leading to the generation of a microenvironment favouring tumor growth and progression. Therefore, it is imperative to explore the expression of miRNA and understand its relevance in lung cancer and development of anti-cancer strategies (anti - miRs, miR mimics and micro RNA sponges). In view of the above, the role of miRNA in lung cancer has been dissected and the associated mechanisms and pathways are discussed in this review.
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                Author and article information

                Contributors
                wangsumei198708@163.com
                linghan36@163.com
                wwanyin@126.com
                Journal
                Mol Carcinog
                Mol Carcinog
                10.1002/(ISSN)1098-2744
                MC
                Molecular Carcinogenesis
                John Wiley and Sons Inc. (Hoboken )
                0899-1987
                1098-2744
                17 January 2022
                April 2022
                : 61
                : 4 ( doiID: 10.1002/mc.v61.4 )
                : 417-432
                Affiliations
                [ 1 ] Department of Oncology, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine Guangzhou Guangdong P.R. China
                [ 2 ] Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome Guangzhou Guangdong P.R. China
                [ 3 ] Guangdong‐Hong Kong‐Macau Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou University of Chinese Medicine Guangzhou Guangdong P.R. China
                [ 4 ] Shanghai University of Traditional Chinese Medicine Shanghai P.R. China
                [ 5 ] Department of Organ Transplantation Second Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong P.R. China
                [ 6 ] Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine Guangzhou Guangdong P.R. China
                [ 7 ] The Second Clinical College of Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine, Guangzhou Guangzhou Guangdong P.R. China
                [ 8 ] Guangdong Provincial Academy of Chinese Medical Sciences Guangzhou Guangdong P.R. China
                Author notes
                [*] [* ] Correspondence

                Sumei Wang, Ling Han, and Wanyin Wu, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, 111 Dade Rd., Guangzhou, Guangdong 510120, P.R. China.

                Email:  wangsumei198708@ 123456163.com linghan36@ 123456163.com , and  wwanyin@ 123456126.com

                Author information
                https://orcid.org/0000-0002-2128-4810
                Article
                MC23389
                10.1002/mc.23389
                9302658
                35040191
                93a3d898-0af5-4947-b4a7-561a536779c9
                © 2022 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 02 December 2021
                : 19 August 2021
                : 10 December 2021
                Page count
                Figures: 8, Tables: 0, Pages: 16, Words: 7924
                Funding
                Funded by: Chinese medicine science and technology research project of Guangdong Provincial Hospital of Chinese Medicine (YN2019MJ09, YN2019QJ06)
                Funded by: Natural Science Foundation of China (81871863)
                Funded by: State key laboratory of Dampness Syndrome of Chinese Medicine Special Fund (SZ2021ZZ29)
                Funded by: Scientific Research Project in Universities of Guangdong Provincial Department of Education (2020KTSCX029)
                Funded by: Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome (ZH2020KF03)
                Funded by: postgraduate research innovation project of Guangzhou University of Chinese Medicine (A1‐2606‐21‐429‐001Z53)
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:21.07.2022

                hepatocellular carcinoma,muc1,solamargine,sorafenib,synergistic anticancer effect

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