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4. Extracellular Matrix–Related Six-lncRNA Signature as a Novel Prognostic Biomarker for Bladder Cancer

Author

Qing, Liangliang, Gu, Peng, Liu, Mingsheng, Shen, Jihong, Liu, Xiaodong, Guang, Runyun, Ke, Kunbin, Huang, Zhuo, Lee, Wenhui, and Zhao, Hui

Subjects
immune-cell infiltration, extracellular matrix, bladder cancer, long noncoding RNA, prognosis, signature, Original Research
Abstract

Introduction Bladder cancer (BC) is the fourth-commones cancer and the sixth-leading cause of cancer-related death among men. However, a lack of reliable biomarkers remains a problem forprognosis and treatment of BC. lncRNAs have been shown to play important roles in various cancers, and have emerged as promising biomarkers for cancer prognosis and treatment. Methods In this study, using univariate and multivariate Cox regression analysis, we examined the differential expression profiles of 1,651 lncRNAs in the TCGA BLCA cohort and created a prognostic gene signature composed of six lncRNAs (for SNHG12, MAFG-DT, ASMTL-AS1, LINC02321, LINC01322, and LINC00922), designed the SMALLL signature. Results The SMALLL signature displayed significant prognostic power for overall survival for BC patients in multiple cohorts. Gene Ontology analysis showed that genes coexpressed with the SMALLL signature were associated with the extracellular matrix network, and immune cell–infiltration analysis showed that activated naïve B cells, regulatory T cells, M0 macrophages, eosinophils, resting memory CD4 T cells and resting NK cells were significantly different in high- and low-risk groups. We also confirmed differential expression of the lncRNAs of the SMALLL signature in BC tissue and paracancer normal tissue by qRT-PCR analysis. Cell-invasion and -migration experiments showed that MAFG-AS1, ASMTL-AS1, LINC02321, and LINC00922 significantly affected cell invasion and migration. Conclusion Our study revealed that the lncRNA signature is an important predictive factor of prognosis and provides a promising biomarker for BC.

Published
2020

6. Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitro and in vivo

Author

Shen, Zhengchao, primary, Wang, Jian, additional, Ke, Kunbin, additional, Chen, Rong, additional, Zuo, Aixue, additional, Zhang, Rongping, additional, Wan, Weiping, additional, Xie, Xingxing, additional, Li, Xuhua, additional, Song, Na, additional, Fu, Hao, additional, Zhang, Zhiwei, additional, Cai, Enli, additional, Shen, Jihong, additional, Zhang, Qingyu, additional, and Shi, Xinan, additional

Published
2021
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8. Econazole nitrate reversed the resistance of breast cancer cells to Adriamycin through inhibiting the PI3K/AKT signaling pathway

Author

Dong, Chao, Chen, Yin, Ma, Jing, Yang, Runxiang, Li, Hongjian, Liu, Rong, You, Dingyun, Luo, Chunxiang, Li, Heng, Yang, Siyuan, Ke, Kunbin, Lin, Marie Chia-mi, and Chen, Ceshi

Subjects
Original Article, Erratum, skin and connective tissue diseases
Abstract

Activation of the phosphoinositide 3 kinase (PI3K)/AKT pathway is frequently implicated in resistance to anticancer therapies. PI3K inhibitors can restore sensitivity to standard breast cancer therapies, including endocrine therapy, HER2-targeted agents, and chemotherapy. Our previous research showed that econazole, a novel PI3Ka inhibitor, inhibits the PI3K/AKT pathway and induces apoptosis in lung cancer cells. In this study, econazole showed significant cytotoxic activity against Adriamycin-resistant breast cancer cells in vitro and in vivo. Additionally, econazole significantly sensitized MDA-MB-231 and MCF-7 cells to Adriamycin via inhibiting the PI3K/AKT pathway. Overexpression of constitutively active AKT1 abolished the function of econazole. The combination of econazole and Adriamycin exerted synergistic inhibitory effects in breast cancer cells in vitro and in vivo. Taken together, the PI3K inhibitor econazole could effectively overcome Adriamycin resistance and showed synergistic effects with chemotherapy on breast cancer.

Published
2019

10. Polyphyllin I, a lethal partner of Palbociclib, suppresses non-small cell lung cancer through activation of p21/CDK2/Rb pathway in vitroand in vivo

Author

Shen, Zhengchao, Wang, Jian, Ke, Kunbin, Chen, Rong, Zuo, Aixue, Zhang, Rongping, Wan, Weiping, Xie, Xingxing, Li, Xuhua, Song, Na, Fu, Hao, Zhang, Zhiwei, Cai, Enli, Shen, Jihong, Zhang, Qingyu, and Shi, Xinan

Abstract

ABSTRACTCyclin-dependent kinases (CDKs) are hyperactive in many cancers and have served as cancer therapeutic targets for decades. Palbociclib (Palb) is the first approved CDK4/6 inhibitor to treat hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Acquired drug resistance is one obstacle of Palb be utilized in other cancer. CDK2 compensation of CDK4/6 loss is one of the causes that cancer cells are resistant to Palb. Hence, targeting multiple CDKs could be a novel strategy to prevent the drug resistance of cancer cells and expand the application of Palb in other cancer. In this study, we initially indicated Polyphyllin I (PPI) significantly inhibits non-small lung cancer cell (NSCLC) proliferation, promotes cell apoptosis in vitroand in vivo. Mechanistically, PPI can inhibit Rb through the p21/CDK2/Rb signaling pathway in NSCLC. A combination of PPI and Palb exerts a significant synergistic anti-cancer ability on NSCLC. Of note, PPI can reverse Palb drug resistance. Herein, we first time demonstrated PPI can disturb CDK2 function through upregulation of p21. The PPI effect on CDK2 provides a choice for a chemotherapeutic strategy for the elimination of NSCLC. Our study highlighted the clinical significance of simultaneously blocking of CDK2 and CDK4/6 for NSCLC treatment.

Published
2021
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11. Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells

Author

Dong, Chao, primary, Yang, Runxiang, additional, Li, Hongjian, additional, Ke, Kunbin, additional, Luo, Chunxiang, additional, Yang, Fang, additional, Shi, Xi-Nan, additional, Zhu, Ying, additional, Liu, Xu, additional, Wong, Man-Hon, additional, Lin, Guimiao, additional, Wang, Xiaomei, additional, Leung, Kwong-Sak, additional, Kung, Hsiang-Fu, additional, Chen, Ceshi, additional, and Lin, Marie Chia-mi, additional

Published
2017
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12. The feasibility of uterine-vaginal axis MRI-based as evaluation of surgical efficacy in women with pelvic organ prolapse.

Author

Wang H, Shen J, Li S, Gao Z, Ke K, and Gu P

Abstract

Background: The aim of this study was to provide a potential surgical efficacy assessment in the treatment of pelvic organ prolapse (POP)., Methods: A retrospective cohort study was performed on magnetic resonance imaging (MRI) imaging data of 16 non-prolapsed (control group) and 30 preoperative and postoperative POP (case group) women from 2019 to 2021 at the First Affiliated Hospital of Kunming Medical University. MRI diagnoses and measures of the relevant anatomical points at rest were used to analyze the healthy control data and the data from POP women before and after surgery., Results: The middle vaginal-PICS line angle (78.12°±15.03° vs. 69.35°±11.51°, 78.12°±15.03° vs. 61.56°±9.58°, P<0.05) and the middle-lower vaginal angle (179.30°±12.96° vs. 161.73°±10.42°, 179.30°±12.96° vs. 147.01°±12.20°, P<0.05) in the preoperative group were significantly larger than those in the control and postoperative groups. Y-axis coordinates of the endocervical orifice (-52.39±15.63 vs. -59.04±11.49 mm, -52.39±15.63 vs. -65.27±7.25 mm, P<0.05), posterior vaginal fornix (-34.25±13.30 vs. -46.69±11.09 mm, -34.25±13.30 vs. -49.93±8.02 mm, P<0.05), the junction of the middle and lower vagina (-0.48±8.65 vs. -11.34±7.33 mm, -0.48±8.65 vs. -10.11±9.77 mm, P<0.05), and anterior vaginal fornix (-23.14±13.71 vs. -34.68±9.07 mm, -23.14±13.71 vs. -38.64±6.48 mm, P<0.05), as well as the x-axes of the junction of the middle and lower parts of the vagina (26.79±6.71 vs. 19.56±5.24, 26.79±6.71 vs. 17.67±5.81, P<0.05), and vaginal introitus (23.39±7.12 vs. 18.55±4.22, 23.39±7.12 vs. 19.00±4.55, P<0.05) in the preoperative group were smaller than those of the control and postoperative groups. Differences between the control and postoperative groups were not statistically significant (P>0.05)., Conclusions: The current study established that the uterine-vaginal axis of POP women moved backward and downward in the coordinate system, as shown on MRI sagittal images. Further, it moved forward and upwards after surgical repair and more closely resembled that of the control group. The uterine-vaginal axis may provide an evaluation of surgical efficacy in women with POP., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1173/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Published
2022
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