RSK2: a promising therapeutic target for the treatment of triple-negative breast cancer

Huynh, My-my; Jayanthan, Aarthi; Pambid, Mary Rose; Los, Gerrit; Dunn, Sandra E.

doi:10.1080/14728222.2020.1709824

Cited by 19 publications

(12 citation statements)

References 14 publications

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“…Having established the circFBXL5/miR-216b axis, we further confirmed miR-216b could target HMGA2. The previous studies reported that HMGA2 could contribute to breast cancer cell metastasis, while inhibit apoptosis [ 36 , 37 ]. In addition, increasing evidences had suggested that HMGA2 could facilitate 5-FU resistance in many cancers, like hepatoma cancer, colorectal cancer and breast cancer [ 21 – 23 , 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis

Zhu

Wang

et al. 2021

Cancer Cell Int

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Background Circular RNAs (circRNAs) have been confirmed to be relevant to the 5-fluorouracil (5-FU) resistance of breast cancer. Nevertheless, how and whether circRNA F-box and leucine-rich repeat protein 5 (circFBXL5) regulates the 5-FU resistance of breast cancer is uncertain. This study aims to explore the function and mechanism of circFBXL5 in the 5-FU resistance of breast cancer. Methods Thirty nine paired breast cancer and normal tissues were harvested. circFBXL5, microRNA-216b (miR-216b) and high-mobility group AT-hook 2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, 5-FU resistance, migration, invasion, and apoptosis were tested via cell counting kit-8 assay, wound healing analysis, transwell analysis, and flow cytometry. The relationship of miR-216b and circFBXL5 or HMGA2 was tested via dual-luciferase reporter analysis and RNA pull-down assay. The impact of circFBXL5 on breast cancer tumor growth in vivo was analyzed via xenograft model. Results circFBXL5 was highly expressed in breast cancer tissues and cells, and was more upregulated in 5-FU-resistant breast cancer cells. Function experiments showed that circFBXL5 knockdown inhibited the 5-FU resistance of breast cancer by inhibiting cell migration, invasion and promoting apoptosis. In the terms of mechanism, miR-216b could be sponged by circFBXL5, and its inhibitor could also reverse the influence of circFBXL5 silencing on the 5-FU resistance of breast cancer cells. In addition, HMGA2 was a target of miR-216b, and its overexpression also reversed the regulation of miR-216b overexpression on the 5-FU resistance of breast cancer. Furthermore, circFBXL5 interference declined breast cancer tumor growth in xenograft model. Conclusion Our data showed that circFBXL5 could promote the 5-FU resistance of breast cancer by regulating miR-216b/HMGA2 axis.

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Section: Discussionmentioning

confidence: 99%

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis

Zhu

Wang

et al. 2021

Cancer Cell Int

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“…Deficient nutrient intake, obesity, and poor eating behaviors have been reported in patients with chronic pain [ 63 ] and dietary changes aimed at reducing body fat or adapting a healthier diet can have a positive impact on chronic pain [ 64 , 65 ]. Diet has been linked to central and peripheral pain pathways, [ 66 , 67 ], and though the mechanisms linking chronic pain and diet are not clear, it increasingly appears that diet and weight management are part of a holistic strategy to manage chronic pain [ 68 , 69 ]. Hydration levels can influence pain perception, highlighting the importance of proper fluid intake [ 70 , 71 ].…”

Section: Introductionmentioning

confidence: 99%

Move to health-a holistic approach to the management of chronic low back pain: an intervention and implementation protocol developed for a pragmatic clinical trial

et al. 2021

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Background The prevalence of chronic pain conditions is growing. Low back pain was the primary cause of disability worldwide out of 156 conditions assessed between 1990 and 2016, according to the Global Burden of Disease Study. Conventional medical approaches have failed to identify effective and long-lasting approaches for the management of chronic pain, and often fail to consider the multiple domains that influence overall health and can contribute to the pain experience. Leading international organizations that focus on pain research have stated the importance of considering these other domains within holistic and multidisciplinary frameworks for treating pain. While the research behind the theoretical link between these domains and chronic pain outcomes has expanded greatly over the last decade, there have been few practical and feasible methods to implement this type of care in normal clinical practice. Methods The purpose of this manuscript is to describe an implementation protocol that is being used to deliver a complex holistic health intervention at multiple sites within a large government health system, as part of a larger multisite trial for patients with chronic low back pain. The Move to Health program developed by the US Army Medical Command was tailored for specific application to patients with low back pain and begins by providing an empirical link between eight different health domains (that include physical, emotional, social, and psychological constructs) and chronic low back pain. Through a six-step process, a health coach leverages motivational interviewing and information from a personal health inventory to guide the patient through a series of conversations about behavioral lifestyle choices. The patient chooses which domains they want to prioritize, and the health coach helps implement the plan with the use of SMART (Specific, Measurable, Attainable, Realistic, Time-bound) goals and a series of resources for every domain, triaged from self-management to specialist referral. Discussion Complex interventions described in clinical trials are often challenging to implement because they lack sufficient details. Implementation protocols can improve the ability to properly deliver trial interventions into regular clinical practice with increased fidelity. Trial registration Implementation of this intervention protocol was developed for a clinical trial that was registered a priori (clinicaltrials.gov #NCT04172038).

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“…Table S2: Molecular docking scores and binding interactions of compounds 1-3, 5, 7, and 12 on the selected drug targets. Figure S1: 1 H, 13 C-NMR and ESI-MS spectra of the known compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

“…Phytochemical analysis of L. shawii led to the isolation of 9 compounds: dehydrocostus lactone (1), costunolide (2), lyciumate (3), catechin (4), aloe emodin (5), emodin (6), emodin-8-O-β-D-glucoside (7), aloe emodine 11-O-rhamnoside (8), and lyciumaside (9) [35]. Similarly, phytochemical investigation of A. vera resin provided 11 compounds including 10-hydroxy aloin A (10) [38], aloinoside B (11) [39], 7-demethylsiderin (12) [40], 6 -O-coumaroylaloesin (13) [41], feroxidin (14) [42], 3-(4-hydroxyphenyl)propanoic acid (15), methyl 3-(4-hydroxyphenyl)propionate (16) [43], 1-(2,4-dihydroxy6-methylphenyl)ethanone (17) [44], p-anisaldehyde (18), salicylaldehyde (19) [45], and p-cresol (20) [46]. All structures of the compounds were confirmed by combined spectroscopic techniques including 1D ( 1 H and 13 C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS) ( Figure S1).…”

Section: Phytochemical Investigationmentioning

confidence: 99%

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing

et al. 2020

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Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (1H and 13C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC50 values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC50 values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC50 = 14.4 µM), 12 (IC50 = 23.3), and 2 (IC50 = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.

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RSK2: a promising therapeutic target for the treatment of triple-negative breast cancer

Cited by 19 publications

References 14 publications

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis

CircFBXL5 promotes the 5-FU resistance of breast cancer via modulating miR-216b/HMGA2 axis

Move to health-a holistic approach to the management of chronic low back pain: an intervention and implementation protocol developed for a pragmatic clinical trial

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing

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