Xiaotan Sanjie Decoction Inhibits Gastric Cancer Cell Proliferation, Migration, and Invasion through lncRNA-ATB and miR-200A

Zhou, Zhe; Chen, Jiabin; Li, Mingqian; Cao, Liping; Chen, Miao; Zhang, Qingqian; Yu, Zhihong; Chai, Kequn

doi:https://doi.org/10.1155/2022/7029182

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Abstract Introduction Methods Results Discussion and Conclusion Data Availability Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

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Volume 2022 | Article ID 7029182 | https://doi.org/10.1155/2022/7029182

Xiaotan Sanjie Decoction Inhibits Gastric Cancer Cell Proliferation, Migration, and Invasion through lncRNA-ATB and miR-200A

Zhe Zhou,^1,2,3Jiabin Chen,^1,2,3Mingqian Li,^2,3Liping Cao,^1,2,3Miao Chen,^2,3Qingqian Zhang,^2,3Zhihong Yu ,^1,2,3and Kequn Chai^1,2,3

Academic Editor: Yue Gu

Received02 Jun 2022

Revised08 Jul 2022

Accepted11 Jul 2022

Published25 Aug 2022

Abstract

This study is aimed at exploring whether Xiaotan Sanjie decoction (XTSJ) inhibits gastric cancer (GC) proliferation and metastasis by regulating lncRNA-ATB expression. qRT-PCR and Western blot were used to analyze lncRNA-ATB and downstream-regulated genes/proteins in human GC cells. CCK8, Edu, and flow cytometry assays were used to detect the inhibitory effect of XTSJ on cell proliferation and apoptosis. Moreover, transwell and wound healing assays were used to detect the inhibitory effect of XTSJ on migration and invasion. qRT-PCR and Western blot were used to detect regulated genes and proteins levels. The HGC-27 cell line was used for follow-up analysis due to the high level of lncRNA-ATB and cell characteristics. XTSJ inhibited the proliferation and metastasis of HGC-27 in a dose-dependent manner. Further research found that XTSJ downregulated lncRNA-ATB, Vimentin, and N-cadherin, while it upregulated miR-200a and E-cadherin in a dose-dependent manner. XTSJ also upregulated Caspase 3, Caspase 9, Bax, and downregulated Bcl-2. Furthermore, XTSJ inhibited tumor growth in vivo and downregulated EMT signaling pathways. These results indicate that XTSJ may affect EMT and Bcl-2 signaling pathways by regulating lncRNA-ATB and miR-200a, thus inhibiting proliferation, migration, and invasion of HGC-27 cells. Therefore, XTSJ may be an effective treatment for the high levels of lncRNA-ATB in GC.

1. Introduction

Gastric cancer (GC) has a poor prognosis and is the leading cause of cancer-related deaths [1]. Research has shown that traditional Chinese medicine can treat cancer [2, 3]. Therefore, studying the molecular pathways of traditional Chinese medicine can effectively enhance GC treatment.

lncRNAs are long-chain noncoding RNAs regulating gene transcription and downstream biological signals in tumors [4, 5]. Preliminarily studies have shown that lncRNAs acts as “sponge” to modulate downstream biological signals by competitively binding or chelating microRNAs [6]. TGF-β-activated lncRNA-ATB can enhance epithelial-mesenchymal transition(EMT)-related metastasis and proliferation by competitively binding to the miR-200 family in certain malignant tumors [7, 8]. Recent research showed that lncRNA-ATB upregulation in GC enhances vascular infiltration and overall survival while lncRNA-ATB silencing inhibits cell proliferation [9]. Therefore, lncRNA-ATB and miR-200a are potential therapeutic targets for GC treatment.

Xiaotan Sanjie decoction (XTSJ) can effectively prolong the survival of GC patients, decrease TGF-β and IL-8 levels, and inhibit the expression of fibroblast activation protein (FAP) [10, 11]. This research aimed to assess whether XTSJ prevents GC proliferation and metastasis by regulating lncRNA-ATB and miR-200a.

2. Material and Methods

2.1. Cell Culture

MKN-45, SNU-1, HGC-27, AGS, and MGC-803 were obtained from the Institute of Biochemistry and Cell Biology at the Chinese Academy of Sciences. The cells were cultured in RPMI-1640 medium with 10% fetal bovine serum (ExCell bio, Shanghai, China).

2.2. Preparation of Drugs

Prof. Wei Pinkang provided the XTSJ. XTSJ components have been described in previous papers. Its active components have been analyzed via HPLC [12]. The 5-fluorouracil (5-Fu) was obtained from Lilly France (Suzhou, China).

2.3. CCK-8 Assay

The GC cells ( cells/well) were reinoculated and treated with XTSJ for 24, 48, and 72 hours. An appropriate amount of CCK-8 solution was added to the sample, then incubated for 2 hours. A SpectraMax i3 microplate reader (Molecular Devices, CA, USA) was used to measure absorbance.

2.4. Ethynyl-2-Deoxyuridine (EdU) Assay

The HGC-27 cells ( cells/well) were reinoculated and treated with XTSJ for 24 hours. EdU (100 μL; 50 μ m) was then added to the sample then co-cultured for 2 hours. Hoechst3342 (5 μg/ml) was stained at room temperature for 20 minutes. An Olympus TH4-200 fluorescence microscope (Olympus, Tokyo, Japan) was used to obtain images.

2.5. Flow Cytometry Assay

The HGC-27 cells ( cells/well) were treated with Annexin V-fluorescein isothiocyanate and propidium iodide (Procell, Wuhan, China) for 15 minutes under a shading environment. BD FACSCanto™ II Flow Cytometry System (BD Biosciences, NJ, USA) was used to detect cell apoptosis.

2.6. Transwell Migration and Invasion Assays

The HGC-27 cells ( cells/well) were reinoculated into the upper chamber coated with Matrigel for invasion assay. For the migration assay, HGC-27 cells ( cells/well) were reinoculated into the upper chamber ( cells/well) without Matrigel. The upper chamber was filled with serum-free medium, while the lower chamber was filled with medium containing 10% FBS. The transwell chambers were fixed with a 4.0% paraformaldehyde solution for 15 minutes, then stained with a 0.1% crystal violet solution for 10 minutes. A Leica DMi1 inverted microscope (Leica, Wetzlar, Germany) was used to obtain images.

2.7. Wound-Healing Assay

The HGC-27 cells ( cells/well) were reinoculated until they reached 90% confluence. A 200 μl sterile pipette tip was then used to scratch the center of each well. A Leica DMi1 inverted microscope was then used to assess the wound after 0, 24, and 48 hours.

2.8. Western Blot

Total protein was extracted from the HGC-27 cells ( cells/well) cells using cell lysate buffer after 24 hours. BCA protein quantitative Kit (Sangon Biotech, Shanghai, China) was used for protein quantitation. Protein concentration was adjusted before protein denaturation. Electrophoresis of the protein sample was conducted on SDS-polyacrylamide gels at 60 V for 3-5 hours. The samples were then transferred onto polyvinylidene difluoride film (Bio-Rad, Hercules, CA, USA) at 300 mA for 90 minutes. The film was blocked with a 5% BSA solution for 90 minutes, then incubated with primary antibodies (E-cadherin (20874-1-AP), Vimentin (60330-1-lg), N-cadherin (22018-1-AP), ZEB-1 (21544-1-AP), Bcl-2 (26593-1-AP), Bax (50599-2-Ig), Caspase 3 (19677-1-AP), Caspase 9 (10380-1-AP), and β-actin (66009-1-lg)) at 4°C overnight. The films were then incubated with secondary antibodies (HRP-conjugated Affinipure Goat Anti-mouse IgG (H + L) (SA00001-1) and HRP-conjugated Affinipure Goat Anti-rabbit IgG (H + L) (SA00001-2)) at room temperature for 60 minutes. These antibodies were obtained from Proteintech™ (Wuhan, China). The proteins were visualized using chemiluminescence. Grayscale analysis of Western blot images was conducted using ImageJ.

2.9. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR)

Total RNA was obtained from the HGC-27 ( cells/well) cells using Trizol reagent after 24 hours. The RNAs were reverse transcribed using the reverse aid first-strand cDNA synthesis Kit (Thermo Fisher Scientific, Ma, USA) to obtain cDNA. A LightCycler® 480 Real-Time PCR System (Roche, Basel, Switzerland) was used for qRT-PCR analysis. Each sample had three replicates. The primer sequences used for amplification are shown in Table 1. Quantitative analysis of each sample was conducted using the 2^-△△Ct method.

2.10. In Vivo Experiment

BALB/c nude mice (6-week-old, female) were reared in a sterile environment. The animal experiment was approved by the Ethics Committee of the Tongde Hospital of Zhejiang Province. The tumor model was established by subcutaneously inoculating the HGC-27 cells ( cells/well) into the right side of mouse back. The mice were treated using intragastric of XTSJ (1 g/kg for low-dose and 2 g/kg for high-dose) or intraperitoneal injection of 5-FU (30 mg/kg) every day. The mice were euthanized after seven days. The tumor tissues were dissected and collected. Pathological examination and SABER-FISH were used to assess the expression of EMT related antibodies and the location of lncRNA-ATB in tissues [13, 14].

2.11. Statistical Analysis

Quantitative data are expressed as . The normally distributed data were analyzed using students’ -test analyzed. Mann–Whitney -test was used to analyze the nonnormally distributed data. Graph-Pad Prism8. 0 software was used for data analysis and drawing charts. , , and represent significant differences.

3. Results

3.1. HGC27 Cell Line as a Model for Drug Intervention of lncRNA-ATB In Vitro

lncRNA-ATB and EMT signal pathway-related genes and proteins in five GC cells were analyzed to find a suitable cell model for in vitro drug intervention of lncRNA-ATB. lncRNA-ATB, Vimentin, and N-cadherin were upregulated in HGC-27 and MKN-45, while miR-200a and E-cadherin were downregulated (Figure 1(a)). Western blot also revealed that ZEB-1, Vimentin, and N-cadherin were upregulated in HGC-27 while E-cadherin was downregulated (Figure 1(b)). However, ZEB-1, Vimentin, and N-cadherin protein levels were relatively low in MKN-45 (a semisuspended cell), while E-cadherin level was relatively high (Figure 1(b)). Moreover, the viability of cells was detected using CCK8. HGC-27 had the lowest IC50 concentration (0.1354 mg/ml), indicating it was the most sensitive to drugs (Figure 1(c)). As a result, HGC-27 was selected as a model for drug intervention in vitro.

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3.2. XTSJ Inhibits Proliferation and Promotes Apoptosis in HGC-27 Cells

Flow cytometry assays showed that apoptosis increased with increasing drug concentration (0 mg/ml, 30.56%; 0.05 mg/ml, 46.23%; 0.1 mg/ml, 50.23%; 0.15 mg/ml, 67.41%; 0.2 mg/ml, 76.16%; 0.3 mg/ml, 83.83%), especially in early apoptosis (Figures 2(b) and 2(c)). EdU assays indicated that the ratio of EdU/Hoechst33342 decreased with increasing XTSJ concentration (0 mg/ml, 59.60%; 0.05 mg/ml, 50.48%; 0.1 mg/ml, 43.93%; 0.15 mg/ml, 31.89%), thus inhibiting proliferation. CCK8 assay showed that XTSJ had an inhibitory effect in a concentration dependent manner () and not time-dependent (Figure 2(a)) (Figures 2(d) and 2(e)). These results suggest that XTSJ can inhibit HGC-27 cell proliferation and promote apoptosis.

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Figure 2

Effects of XTSJ on HGC-27 cells proliferation and apoptosis. (a) Effect of different concentrations of XTSJ in the viability of HGC-27 cells. (b) Effects of XTSJ on cells apoptosis were detected by flow cytometry, and (c) the cell apoptosis rate was quantified. (d) EdU assay was performed to observe cell proliferation intervened by XTSJ; blue-labeled (Hoechst 33324) is the nucleus, green-labeled implies the cells undergoing the proliferation process; and (e) the EdU/Hoechst 33324 ratio was quantified. ; ; .

3.3. XTSJ Inhibits Migration and Invasion in HGC-27 Cells

Transwell assays demonstrated that XTSJ significantly reduced cell number in the migration assays at high concentrations (0.15 mg/ml). XTSJ also significantly reduced cell number in the invasion assays in a dose-dependent effect (Figures 3(a) and 3(b)). Wound healing assays found that XTSJ effectively maintained the wound healing range and inhibited cell invasion (Figures 3(c) and 3(d)). These results suggest that XTSJ can effectively inhibit HGC-27 metastasis.

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3.4. XTSJ Inhibits the Expression of lncRNA and Related EMT and Bcl-2 Signaling Pathways

lncRNA-ATB and downstream-regulated genes and proteins were analyzed using qRT-PCR and Western blotting to reveal how XTSJ inhibits the proliferation and metastasis of HGC-27. qRT-PCR showed that XTSJ reduced the levels of lncRNA-ATB, Vimentin, and N-cadherin while increasing miR-200a and E-cadherin levels in a dose-dependent effect (Figure 4(a)). Similarly, Western blot assays showed that XTSJ reduced ZEB-1, Vimentin, and N-cadherin levels while increasing E-cadherin levels (Figures 4(b) and 4(c)). Western blot also showed that XTSJ reduced Bcl-2 level while it increased Caspase 3, Caspase 9, and Bax levels (Figures 4(d) and 4(e)). These results suggest that XTSJ affects EMT and Bcl-2 signal pathways by downregulating lncRNA-ATB and upregulating miR-200a.

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Figure 4

Effects of XTSJ on gastric cancer-related mRNA and protein expression. (a) qRT-PCR analysis of lncRNA-ATB, Vimentin, E-cadherin, N-cadherin, and miR-200a after intervention with XTSJ. (b) Western blotting based on detection of ZEB-1, Vimentin, E-cadherin, and N-cadherin after intervention with XTSJ. (c) The relative protein was carried out with β-actin as an internal reference. (d) Western blotting based on detection of Bcl-2, Bax, Caspase 3, and Caspase 9 after intervention with XTSJ. (e) The relative protein was carried out with β-actin as an internal reference. ; ; .

3.5. The Effect of XTSJ on GC In Vivo

Pharmacodynamic analysis was conducted using HGC-27 transplanted tumor nude mice model. XTSJ inhibited the transplanted tumors in mice, similar to chemotherapeutic drugs (5-FU) (Figures 5(a) and 5(b)). SABER-FISH results showed that lncRNA-ATB was upregulated in the model group while it was downregulated in XTSJ group (Figure 5(c)). Immunohistochemical (IHC) analysis showed that XTSJ reduced the levels of antibodies, such as Ki67, Vimentin, and N-cadherin, while it increased E-cadherin levels (Figure 5(d)). These results indicate that XTSJ can affect EMT signaling pathway in vivo (Figure 6).

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Figure 6

Molecular mechanism of XTSJ. The corresponding mechanism may be related to XTSJ reducing LncRNA-ATB and increasing miR-200a competing with it to reduce the expression of downstream ZEB-1 and reverse EMT. The process of reversing EMT showed decreased expression of Vimentin and N-cadherin associated with mesenchymal phenotype and increased E-cadherin expression associated with an epithelial phenotype. In addition, XTSJ could reduce Bcl-2, increase Bax, Caspase 3, and Caspase 9 to induce apoptosis.

4. Discussion and Conclusion

Gastric cancer (GC) has a poor prognosis, especially GC cells at low to medium differentiation stages that easily undergo proliferation, migration, invasion, and tumorigenesis [15]. Therefore, studies should assess the biological mechanism of proliferation and metastasis in GC.

lncRNA-ATB (TGF-β activated long-chain non-coding RNA) >200 nucleotides is located on chromosome 14, and it is related to the occurrence and progression of tumors [16]. lncRNA-ATB is improperly expressed in several cancers, particularly liver cancer [17], colon cancer [18, 19], pancreatic cancer [20], lung cancer [21, 22], breast cancer [23], and ovarian cancer [24, 25], based on research incorporating clinical correlation. Moreover, lncRNA-ATB is related to the prognosis of malignant tumors, including tumor stage, invasion, and metastasis, which directly or indirectly affect the recurrence and overall survival[26]. lncRNA-ATB is also a promising diagnostic index or an index related to drug resistance in some tumors [26–29].

Similarly, lncRNA-ATB was remarkably expressed in GC cells than in adjacent tissues. Increased lncRNA-ATB increases the infiltration depth, distant metastasis, and late tumor lymph node metastasis, affecting the overall survival of GC patients [30]. lncRNAs may act as sponges by competitively binding to microRNAs (miRNAs), thereby inhibiting the active functions [31]. Moreover, lncRNA-ATB silencing can upregulate miR-200 family and induce apoptosis through Bcl-2/caspase 3 pathway in lung cancer and prostate cancer [7, 21]. lncRNA-ATB can also upregulate ZEB1 and ZEB2 by competitively binding to miR-200 family in various tumors [32, 33], resulting in proliferation, migration, and invasion. However, lncRNA-ATB silencing can significantly inhibit ZEB1 and ZEB2 expression, thus inhibiting cell migration and invasion [17, 34]. These results indicate that lncRNA-ATB can affect EMT by competitively binding with miR-200a, thus promoting tumor metastasis in GC [35, 36]. Type I cadherin (epithelial cadherin and E-cadherin) is transformed into N-cadherin and Vimentin (mainly expressed in mesenchymal cells) during EMT [37]. In this study, HGC-27 was selected for follow-up experiments because it had lower E-cadherin and miR-200a levels and higher lncRNA-ATB, Vimentin, N-cadherin, and ZEB-1 levels. XTSJ has been proven in previous research to suppress proliferation, angiogenesis, invasion, and migration [10, 12, 38, 39]. This might be due to the fact that XTSJ lowers lncRNA-ATB and promotes competitive binding to miR-200a, lowering ZEB-1-mediated EMT and Bcl-2-mediated apoptosis. Reduced levels of Vimentin and N-cadherin associated with a mesenchymal phenotype and increasing levels of E-cadherin associated with an epithelial phenotype defined EMT reversal. However, more research should be conducted to identify the major target and effector chemicals of XTSJ that inhibit lncRNA-ATB expression. Furthermore, no research has demonstrated XTSJ’s therapeutic effectiveness or associated biomolecular signals in human GC.

In conclusion, XTSJ may affect EMT and Bcl-2 signaling pathways by regulating lncRNA-ATB and miR-200a, thus inhibiting proliferation, migration, and invasion of HGC-27 cells. Therefore, XTSJ may be an effective treatment for the high level of lncRNA-ATB in GC.

Data Availability

The data used to support the findings of this study are included within the article.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Cai KQ, Yu ZH, and Zhou Z designed this research. Zhou Z, Chen JB, Li MQ, Cao LP, Chen M, and Zhang QQ participated in the implementation of the experiment. Zhou Z, Li MQ, Yu ZH, and Cai KQ wrote and proofread manuscript. Zhou Z and Chen JB contributed equally to this work.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant nos: 82074093, 81673809, and 81673781), Natural Science Foundation of Zhejiang Province (Grant no: LY19H280005), and Zhejiang Traditional Chinese Medicine (Grant nos: 2020ZX003 and 2016ZQ002).

References

J. Machlowska, J. Baj, M. Sitarz, R. Maciejewski, and R. Sitarz, “Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies,” International Journal of Molecular Sciences, vol. 21, no. 11, 2020.
View at: Publisher Site | Google Scholar
K. Wang, Q. Chen, Y. Shao et al., “Anticancer activities of TCM and their active components against tumor metastasis,” Biomedicine & Pharmacotherapy, vol. 133, article 111044, 2021.
View at: Publisher Site | Google Scholar
L. Yang, J. Li, Z. Hu et al., “A systematic review of the mechanisms underlying treatment of gastric precancerous lesions by traditional Chinese medicine,” Evidence-Based Complementary and Alternative Medicine, vol. 2020, Article ID 9154738, 12 pages, 2020.
View at: Publisher Site | Google Scholar
N. G. Lintner and J. H. D. Cate, “Regulating the ribosome: a spotlight on RNA dark matter,” Molecular Cell, vol. 54, no. 1, pp. 1-2, 2014.
View at: Publisher Site | Google Scholar
C. P. Ponting, P. L. Oliver, and W. Reik, “Evolution and functions of long noncoding RNAs,” Cell, vol. 136, no. 4, pp. 629–641, 2009.
View at: Publisher Site | Google Scholar
M. Cesana, D. Cacchiarelli, I. Legnini et al., “A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA,” Cell, vol. 147, no. 2, pp. 358–369, 2011.
View at: Publisher Site | Google Scholar
H. Lin, L. Yang, F. Tian et al., “Up-regulated lncRNA-ATB regulates the growth and metastasis of cholangiocarcinoma via miR-200c signals,” OncoTargets and Therapy, vol. 12, pp. 7561–7571, 2019.
View at: Publisher Site | Google Scholar
J. H. Yuan, F. Yang, F. Wang et al., “A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma,” Cancer Cell, vol. 25, no. 5, pp. 666–681, 2014.
View at: Publisher Site | Google Scholar
Y. Chen, G. Wei, H. Xia, Q. Tang, and F. Bi, “Long noncoding RNAATB promotes cell proliferation, migration and invasion in gastric cancer,” Molecular Medicine Reports, vol. 17, no. 1, pp. 1940–1946, 2018.
View at: Publisher Site | Google Scholar
J. Shi and P. K. Wei, “Xiaotan Sanjie decoction inhibits interleukin-8-induced metastatic potency in gastric cancer,” World Journal of Gastroenterology: WJG, vol. 21, no. 5, pp. 1479–1487, 2015.
View at: Publisher Site | Google Scholar
M. Ye, D. Z. Sun, and P. K. Wei, “Inhibitory effect of Xiaotan Sanjie recipe on the microsatellite instability of orthotopic transplantation tumor in MKN-45 human gastric cancer nude mice,” Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi= Chinese Journal of Integrated Traditional and Western Medicine, vol. 34, no. 5, pp. 592–596, 2014.
View at: Google Scholar
B. Yan, L. Liu, Y. Zhao et al., “Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells,” World Journal of Gastroenterology: WJG, vol. 20, no. 36, pp. 13105–13118, 2014.
View at: Publisher Site | Google Scholar
J. Y. Kishi, S. W. Lapan, B. J. Beliveau et al., “SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues,” Nature Methods, vol. 16, no. 6, pp. 533–544, 2019.
View at: Publisher Site | Google Scholar
M. Lai, L. Liu, L. Zhu et al., “Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy,” Annals of Translational Medicine, vol. 9, no. 16, p. 1304, 2021.
View at: Publisher Site | Google Scholar
G. L. Sun, Z. Li, W. Z. Wang et al., “miR-324-3p promotes gastric cancer development by activating Smad4-mediated Wnt/beta-catenin signaling pathway,” Journal of Gastroenterology, vol. 53, no. 6, pp. 725–739, 2018.
View at: Publisher Site | Google Scholar
J. C. Wang, Z. Buser, D. E. Fish et al., “Intraoperative death during cervical spinal surgery: a retrospective multicenter study,” Global Spine Journal, vol. 7, Supplement 1, pp. 127S–131S, 2017.
View at: Publisher Site | Google Scholar
F. Chen, Y. Li, Y. Feng, X. He, and L. Wang, “Evaluation of antimetastatic effect of lncRNA-ATB siRNA delivered using ultrasound-targeted microbubble destruction,” DNA and Cell Biology, vol. 35, no. 8, pp. 393–397, 2016.
View at: Publisher Site | Google Scholar
T. Iguchi, R. Uchi, S. Nambara et al., “A long noncoding RNA, lncRNA-ATB, is involved in the progression and prognosis of colorectal cancer,” Anticancer Research, vol. 35, no. 3, pp. 1385–1388, 2015.
View at: Google Scholar
B. Yue, S. Qiu, S. Zhao et al., “LncRNA‐ATB mediated E‐cadherin repression promotes the progression of colon cancer and predicts poor prognosis,” Journal of Gastroenterology and Hepatology, vol. 31, no. 3, pp. 595–603, 2016.
View at: Publisher Site | Google Scholar
S. Qu, X. Yang, W. Song et al., “Downregulation of lncRNA-ATB correlates with clinical progression and unfavorable prognosis in pancreatic cancer,” Tumor Biology, vol. 37, no. 3, pp. 3933–3938, 2016.
View at: Publisher Site | Google Scholar
T. Wang, X. Tang, and Y. Liu, “LncRNA-ATB promotes apoptosis of non-small cell lung cancer cells through miR-200a/beta-catenin,” Journal of BUON, vol. 24, no. 6, pp. 2280–2286, 2019.
View at: Google Scholar
L. Wei, T. Wu, P. He, J. L. Zhang, and W. Wu, “LncRNA ATB promotes the proliferation and metastasis of lung cancer via activation of the p38 signaling pathway,” Oncology Letters, vol. 16, no. 3, pp. 3907–3912, 2018.
View at: Publisher Site | Google Scholar
Y. Zhang, J. Li, S. Jia, Y. Wang, Y. Kang, and W. Zhang, “Down-regulation of lncRNA-ATB inhibits epithelial-mesenchymal transition of breast cancer cells by increasing miR-141-3p expression,” Biochemistry and Cell Biology, vol. 97, no. 2, pp. 193–200, 2019.
View at: Publisher Site | Google Scholar
D. Yuan, H. Qian, T. Guo et al., “LncRNA-ATB promotes the tumorigenesis of ovarian cancer via targeting miR-204-3p,” OncoTargets and Therapy, vol. 13, pp. 573–583, 2020.
View at: Publisher Site | Google Scholar
D. Yuan, X. Zhang, Y. Zhao et al., “Role of lncRNA-ATB in ovarian cancer and its mechanisms of action,” Experimental and Therapeutic Medicine, vol. 19, no. 2, pp. 965–971, 2020.
View at: Publisher Site | Google Scholar
F. Tang, Y. Xu, H. Wang, E. Bian, and B. Zhao, “LncRNA-ATB in cancers: what do we know so far?” Molecular Biology Reports, vol. 47, no. 5, pp. 4077–4086, 2020.
View at: Publisher Site | Google Scholar
N. E. El-Ashmawy, F. Z. Hussien, O. A. El-Feky, S. M. Hamouda, and G. M. Al-Ashmawy, “Serum LncRNA-ATB and FAM83H-AS1 as diagnostic/prognostic non-invasive biomarkers for breast cancer,” Life Sciences, vol. 259, article 118193, 2020.
View at: Publisher Site | Google Scholar
S. J. Shi, L. J. Wang, B. Yu, Y. H. Li, Y. Jin, and X. Z. Bai, “Lncrna-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer,” Oncotarget, vol. 6, no. 13, pp. 11652–11663, 2015.
View at: Publisher Site | Google Scholar
W. Tang, X. Yu, R. Zeng, and L. Chen, “lncRNA-ATB promotes cisplatin resistance in lung adenocarcinoma cells by targeting the miR-200a/beta-catenin pathway,” Cancer Management and Research, vol. 12, p. 2001, 2020.
View at: Publisher Site | Google Scholar
T. Saito, J. Kurashige, S. Nambara et al., “A long non-coding RNA activated by transforming growth Factor-β is an independent prognostic marker of gastric cancer,” Annals of Surgical Oncology, vol. 22, Supplement 3, pp. S915–S922, 2015.
View at: Publisher Site | Google Scholar
C. L. Chen, Y. W. Tseng, J. C. Wu et al., “Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation,” Biomaterials, vol. 44, pp. 71–81, 2015.
View at: Publisher Site | Google Scholar
U. Burk, J. Schubert, U. Wellner et al., “A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells,” EMBO Reports, vol. 9, no. 6, pp. 582–589, 2008.
View at: Publisher Site | Google Scholar
C. C. Ma, Z. Xiong, G. N. Zhu et al., “Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a,” Journal of Experimental & Clinical Cancer Research, vol. 35, no. 1, p. 90, 2016.
View at: Publisher Site | Google Scholar
C. P. Bracken, P. A. Gregory, N. Kolesnikoff et al., “A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition,” Cancer Research, vol. 68, no. 19, pp. 7846–7854, 2008.
View at: Publisher Site | Google Scholar
J. Kozak, A. Forma, M. Czeczelewski et al., “Inhibition or reversal of the epithelial-mesenchymal transition in gastric cancer: pharmacological approaches,” International Journal of Molecular Sciences, vol. 22, no. 1, 2020.
View at: Publisher Site | Google Scholar
H. Zhao, H. Hu, B. Chen et al., “Overview on the role of E-cadherin in gastric cancer: dysregulation and clinical implications,” Frontiers in Molecular Biosciences, vol. 8, article 689139, 2021.
View at: Publisher Site | Google Scholar
J. Li, B. Yang, Q. Zhou et al., “Autophagy promotes hepatocellular carcinoma cell invasion through activation of epithelial-mesenchymal transition,” Carcinogenesis, vol. 34, no. 6, pp. 1343–1351, 2013.
View at: Publisher Site | Google Scholar
C. J. Li, P. K. Wei, and B. L. Yue, “Study on the mechanism of Xiaotan Sanjie recipe for inhibiting proliferation of gastric cancer cells,” Journal of Traditional Chinese Medicine, vol. 30, no. 4, pp. 249–253, 2010.
View at: Google Scholar
J. Shi, Y. Lu, and P. Wei, “Xiaotan Sanjie decoction inhibits angiogenesis in gastric cancer through Interleukin-8-linked regulation of the vascular endothelial growth factor pathway,” Journal of Ethnopharmacology, vol. 189, pp. 230–237, 2016.
View at: Publisher Site | Google Scholar

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