Skip to main content
Erschienen in: Cancer Chemotherapy and Pharmacology 5/2016

07.04.2016 | Original Article

Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer

verfasst von: Chao Shang, Yan Guo, Jiaxing Zhang, Baojun Huang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Urothelial carcinoma associated 1 (UCA1) gene is a long noncoding RNA (lncRNA), which shows expression and function abnormality in some kinds of malignant cancers. This study aimed to investigate its clinical significance and to examine its regulative effects of malignant proliferation and chemosensitivity to doxorubicin in gastric cancer cells.

Methods

The expression of UCA1 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for disease-free survival. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. The expression of cleaved PARP and Bcl-2 protein was examined by Western blot.

Results

UCA1 was highly expressed in gastric cancer tissues and cells, and its high expression level had a positive correlation with some malignant pathological characteristics of gastric cancer, such as higher grade and poor differentiation. Moreover, UCA1 was an independent prognostic biomarker of disease-free survival for gastric cancer patients. Silence of UCA1 could significantly inhibit the cell proliferation of gastric cancer BGC-823 and SGC7901 cells. The chemotherapy resistance to adriamycin of SGC7901/ADR cells was depressed by UCA1 silence, and IC50 for adriamycin presented a conspicuous depression. UCA1 silence advanced apoptosis induced by adriamycin in SGC7901/ADR cells, up-regulated cleaved PARP protein expression and depressed the expression of anti-apoptosis protein Bcl-2. These results demonstrated that chemotherapy resistance changes induced by UCA1 silence might be mediated by the cell apoptosis pathway.

Conclusions

In summary, lncRNA UCA1 was an independent prognostic biomarker of disease-free survival in gastric cancer patients and acted as an oncogene to regulate the malignant proliferation and resistance to adriamycin in gastric cancer cells. UCA1 might provide a new potential therapeutic target and stratagem for gastric cancer.
Literatur
1.
Zurück zum Zitat Sugano K (2015) Screening of gastric cancer in Asia. Best Pract Res Clin Gastroenterol 29(6):895–905CrossRefPubMed Sugano K (2015) Screening of gastric cancer in Asia. Best Pract Res Clin Gastroenterol 29(6):895–905CrossRefPubMed
2.
Zurück zum Zitat Newton AD, Datta J, Loaiza-Bonilla A, Karakousis GC, Roses RE (2015) Neoadjuvant therapy for gastric cancer: current evidence and future directions. J Gastrointest Oncol 6(5):534–543PubMedPubMedCentral Newton AD, Datta J, Loaiza-Bonilla A, Karakousis GC, Roses RE (2015) Neoadjuvant therapy for gastric cancer: current evidence and future directions. J Gastrointest Oncol 6(5):534–543PubMedPubMedCentral
3.
Zurück zum Zitat Xu XD, Li KR, Li XM, Yao J, Qin J, Yan B (2014) Long non-coding RNAs: new players in ocular neovascularization. Mol Biol Rep 41(7):4493–4505CrossRefPubMed Xu XD, Li KR, Li XM, Yao J, Qin J, Yan B (2014) Long non-coding RNAs: new players in ocular neovascularization. Mol Biol Rep 41(7):4493–4505CrossRefPubMed
4.
Zurück zum Zitat Zhao Y, Feng G, Wang Y, Yue Y, Zhao W (2014) Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. Int J Clin Exp Pathol 7(11):7643–7652PubMedPubMedCentral Zhao Y, Feng G, Wang Y, Yue Y, Zhao W (2014) Regulation of apoptosis by long non-coding RNA HIF1A-AS1 in VSMCs: implications for TAA pathogenesis. Int J Clin Exp Pathol 7(11):7643–7652PubMedPubMedCentral
5.
Zurück zum Zitat Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32(12):1628–1635CrossRefPubMed Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32(12):1628–1635CrossRefPubMed
6.
Zurück zum Zitat Modali SD, Parekh VI, Kebebew E, Agarwal SK (2015) Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors. Mol Endocrinol 29(2):224–237CrossRefPubMedPubMedCentral Modali SD, Parekh VI, Kebebew E, Agarwal SK (2015) Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic neuroendocrine tumors. Mol Endocrinol 29(2):224–237CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q, Yang M (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290(7):3925–3935CrossRefPubMedPubMedCentral Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q, Yang M (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290(7):3925–3935CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Li HJ, Li X, Pang H, Pan JJ, Xie XJ, Chen W (2015) Long non-coding RNA UCA1 promotes glutamine metabolism by targeting miR-16 in human bladder cancer. Jpn J Clin Oncol 45(11):1055–1063CrossRefPubMed Li HJ, Li X, Pang H, Pan JJ, Xie XJ, Chen W (2015) Long non-coding RNA UCA1 promotes glutamine metabolism by targeting miR-16 in human bladder cancer. Jpn J Clin Oncol 45(11):1055–1063CrossRefPubMed
9.
Zurück zum Zitat Na XY, Liu ZY, Ren PP, Yu R, Shang XS (2015) Long non-coding RNA UCA1 contributes to the progression of prostate cancer and regulates proliferation through KLF4-KRT6/13 signaling pathway. Int J Clin Exp Med 8(8):12609–12616PubMedPubMedCentral Na XY, Liu ZY, Ren PP, Yu R, Shang XS (2015) Long non-coding RNA UCA1 contributes to the progression of prostate cancer and regulates proliferation through KLF4-KRT6/13 signaling pathway. Int J Clin Exp Med 8(8):12609–12616PubMedPubMedCentral
10.
Zurück zum Zitat Tuo YL, Li XM, Luo J (2015) Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur Rev Med Pharmacol Sci 19(18):3403–3411PubMed Tuo YL, Li XM, Luo J (2015) Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur Rev Med Pharmacol Sci 19(18):3403–3411PubMed
11.
Zurück zum Zitat Zheng Q, Wu F, Dai WY, Zheng DC, Zheng C, Ye H, Zhou B, Chen JJ, Chen P (2015) Aberrant expression of UCA1 in gastric cancer and its clinical significance. Clin Transl Oncol 17(8):640–646CrossRefPubMed Zheng Q, Wu F, Dai WY, Zheng DC, Zheng C, Ye H, Zhou B, Chen JJ, Chen P (2015) Aberrant expression of UCA1 in gastric cancer and its clinical significance. Clin Transl Oncol 17(8):640–646CrossRefPubMed
12.
Zurück zum Zitat Shang C, Guo Y, Hong Y, Liu YH, Xue YX (2015) MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol Biol Rep 42(3):721–727CrossRefPubMed Shang C, Guo Y, Hong Y, Liu YH, Xue YX (2015) MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol Biol Rep 42(3):721–727CrossRefPubMed
13.
Zurück zum Zitat Zhang Y, Qu X, Li C, Fan Y, Che X, Wang X, Cai Y, Hu X, Liu Y (2015) miR-103/107 modulates multidrug resistance in human gastric carcinoma by downregulating Cav-1. Tumour Biol 36(4):2277–2285CrossRefPubMed Zhang Y, Qu X, Li C, Fan Y, Che X, Wang X, Cai Y, Hu X, Liu Y (2015) miR-103/107 modulates multidrug resistance in human gastric carcinoma by downregulating Cav-1. Tumour Biol 36(4):2277–2285CrossRefPubMed
14.
Zurück zum Zitat Alaimo S, Giugno R, Pulvirenti A (2014) ncPred: ncRNA-disease association prediction through tripartite network-based inference. Front Bioeng Biotechnol 2:71CrossRefPubMedPubMedCentral Alaimo S, Giugno R, Pulvirenti A (2014) ncPred: ncRNA-disease association prediction through tripartite network-based inference. Front Bioeng Biotechnol 2:71CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Fang TT, Sun XJ, Chen J, Zhao Y, Sun RX, Ren N, Liu BB (2014) Long non-coding RNAs are differentially expressed in hepatocellular carcinoma cell lines with differing metastatic potential. Asian Pac J Cancer Prev 15(23):10513–10524CrossRefPubMed Fang TT, Sun XJ, Chen J, Zhao Y, Sun RX, Ren N, Liu BB (2014) Long non-coding RNAs are differentially expressed in hepatocellular carcinoma cell lines with differing metastatic potential. Asian Pac J Cancer Prev 15(23):10513–10524CrossRefPubMed
16.
Zurück zum Zitat Nie F, Sun M, Yang J, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH, Shu YQ (2015) Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther 14(1):268–277CrossRefPubMed Nie F, Sun M, Yang J, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH, Shu YQ (2015) Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther 14(1):268–277CrossRefPubMed
17.
Zurück zum Zitat Wang Y, Liu X, Zhang H, Sun L, Zhou Y, Jin H, Zhang H, Zhang H, Liu J, Guo H, Nie Y, Wu K, Fan D, Zhang H, Liu L (2014) Hypoxia-inducible lncRNA-AK058003 promotes gastric cancer metastasis by targeting γ-synuclein. Neoplasia 16(12):1094–1106CrossRefPubMedPubMedCentral Wang Y, Liu X, Zhang H, Sun L, Zhou Y, Jin H, Zhang H, Zhang H, Liu J, Guo H, Nie Y, Wu K, Fan D, Zhang H, Liu L (2014) Hypoxia-inducible lncRNA-AK058003 promotes gastric cancer metastasis by targeting γ-synuclein. Neoplasia 16(12):1094–1106CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, Sun Y (2014) BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett 8(5):1947–1952PubMedPubMedCentral Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, Sun Y (2014) BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett 8(5):1947–1952PubMedPubMedCentral
19.
Zurück zum Zitat Banet G, Bibi O, Matouk I, Ayesh S, Laster M, Kimber KM, Tykocinski M, de Groot N, Hochberg A, Ohana P (2000) Characterization of human and mouse H19 regulatory sequences. Mol Biol Rep 27(3):157–165CrossRefPubMed Banet G, Bibi O, Matouk I, Ayesh S, Laster M, Kimber KM, Tykocinski M, de Groot N, Hochberg A, Ohana P (2000) Characterization of human and mouse H19 regulatory sequences. Mol Biol Rep 27(3):157–165CrossRefPubMed
20.
Zurück zum Zitat Kraus TF, Greiner A, Guibourt V, Lisec K, Kretzschmar HA (2015) Identification of stably expressed lncRNAs as valid endogenous controls for profiling of human glioma. J Cancer 6(2):111–119CrossRefPubMedPubMedCentral Kraus TF, Greiner A, Guibourt V, Lisec K, Kretzschmar HA (2015) Identification of stably expressed lncRNAs as valid endogenous controls for profiling of human glioma. J Cancer 6(2):111–119CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Zhao W, Dong S, Duan B, Chen P, Shi L, Gao H, Qi H (2015) HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy. Am J Transl Res 7(7):1295–1302PubMedPubMedCentral Zhao W, Dong S, Duan B, Chen P, Shi L, Gao H, Qi H (2015) HOTAIR is a predictive and prognostic biomarker for patients with advanced gastric adenocarcinoma receiving fluorouracil and platinum combination chemotherapy. Am J Transl Res 7(7):1295–1302PubMedPubMedCentral
22.
Zurück zum Zitat Sun J, Song Y, Chen X, Zhao J, Gao P, Huang X, Xu H, Wang Z (2015) Novel long non-coding RNA RP11-119F7.4 as a potential biomarker for the development and progression of gastric cancer. Oncol Lett 10(1):115–120PubMedPubMedCentral Sun J, Song Y, Chen X, Zhao J, Gao P, Huang X, Xu H, Wang Z (2015) Novel long non-coding RNA RP11-119F7.4 as a potential biomarker for the development and progression of gastric cancer. Oncol Lett 10(1):115–120PubMedPubMedCentral
23.
Zurück zum Zitat Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF (2006) Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res 12(16):4851–4858CrossRefPubMed Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF (2006) Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res 12(16):4851–4858CrossRefPubMed
24.
Zurück zum Zitat Chen S, Shao C, Xu M, Ji J, Xie Y, Lei Y, Wang X (2015) Macrophage infiltration promotes invasiveness of breast cancer cells via activating long non-coding RNA UCA1. Int J Clin Exp Pathol 8(8):9052–9061PubMedPubMedCentral Chen S, Shao C, Xu M, Ji J, Xie Y, Lei Y, Wang X (2015) Macrophage infiltration promotes invasiveness of breast cancer cells via activating long non-coding RNA UCA1. Int J Clin Exp Pathol 8(8):9052–9061PubMedPubMedCentral
25.
Zurück zum Zitat Wang F, Zhou J, Xie X, Hu J, Chen L, Hu Q, Guo H, Yu C (2015) Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1in human ovarian cancer cells. Neoplasma 62(3):432–438CrossRefPubMed Wang F, Zhou J, Xie X, Hu J, Chen L, Hu Q, Guo H, Yu C (2015) Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1in human ovarian cancer cells. Neoplasma 62(3):432–438CrossRefPubMed
26.
Zurück zum Zitat Yang C, Li X, Wang Y, Zhao L, Chen W (2012) Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene 496(1):8–16CrossRefPubMed Yang C, Li X, Wang Y, Zhao L, Chen W (2012) Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells. Gene 496(1):8–16CrossRefPubMed
27.
Zurück zum Zitat Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y (2014) Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J 281(7):1750–1758CrossRefPubMed Fan Y, Shen B, Tan M, Mu X, Qin Y, Zhang F, Liu Y (2014) Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling. FEBS J 281(7):1750–1758CrossRefPubMed
28.
Zurück zum Zitat Hong Y, Shang C, Xue YX, Liu YH (2015) Silencing of Bmi-1 gene enhances chemotherapy sensitivity in human glioblastoma cells. Med Sci Monit 21:1002–1007CrossRefPubMedPubMedCentral Hong Y, Shang C, Xue YX, Liu YH (2015) Silencing of Bmi-1 gene enhances chemotherapy sensitivity in human glioblastoma cells. Med Sci Monit 21:1002–1007CrossRefPubMedPubMedCentral
Metadaten
Titel
Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer
verfasst von
Chao Shang
Yan Guo
Jiaxing Zhang
Baojun Huang
Publikationsdatum
07.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 5/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3029-3

Weitere Artikel der Ausgabe 5/2016

Cancer Chemotherapy and Pharmacology 5/2016 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.