본문 바로가기
KERD
논문KCI 등재

LncRNA LINC01232 Enhances Proliferation, Angiogenesis, Migration and Invasion of Colon Adenocarcinoma Cells by Downregulating miR-181a-5p

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류생물학

초록

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

Abstract

LncRNAs play crucial roles in the progression of colon adenocarcinoma (COAD), but the role of LINC01232 in COAD has not received much attention. The present study was designed to explore the related mechanisms of LINC01232 in the progression of COAD. LINC01232, miR-181a-5p, p53, c-myc, Bcl-2, cyclin D1, p16, Bax, VEGF, E-cadherin, vimentin, N-cadherin and SDAD1 expressions were determined by western blot and qRT-PCR. CCK-8, tubule formation, and Transwell assays were employed to detect proliferation, angiogenesis, and migration/invasion of COAD cells, respectively. The relationship between LINC01232 and miR-181a-5p was predicted by LncBase Predicted v.2, and then verified through dual luciferase reporter gene assay. According to the results, LINC01232 was highly expressed in COAD cells and enhanced proliferation, angiogenesis, migration, and invasion of COAD cells. Downregulated LINC01232 promoted expression of p53 and p16, and inhibited c-myc, Bcl-2 and cyclin D1 expressions in COAD cells, while upregulation of LINC01232 generated the opposite effects. LINC01232 was negatively correlated with miR-181a-5p while downregulated miR181a-5p could reverse the effects of siLINC01232 on cell proliferation, angiogenesis, migration, and invasion. Similarly, miR-181a-5p mimic could also offset the effect of LINC01232 overexpression. SiLINC01232 increased the expressions of Bax and E-cadherin, and decreased the expressions of VEGF, vimentin, N-cadherin and SDAD1, which were partially attenuated by miR-181a-5p inhibitor. Collectively, LINC01232 enhances the proliferation, migration, invasion, and angiogenesis of COAD cells by decreasing miR-181a-5p expression.

참고문헌 (38)

  1. McLaughlin C, "Adjuvant radiation therapy for T4 non-rectal colon adenocarcinoma provides a cause-specific survival advantage: A SEER database analysis", Radiother. Oncol, 133, pp.50~53 (2019)
  2. Bray F, "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J. Clin, 68, pp.394~424 (2018)
  3. Wei Z, "Analysis of risk factors on vascular invasion in patients with early gastric cancer", Zhonghua Wei Chang Wai Ke Za Zhi, 21, pp.803~807 (2018)
  4. Liu J, "Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNAsequencing", Tumour Biol, 39, pp.1010428317714899~ (2017)
  5. Lieberman DA, "Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer", Gastroenterology, 143, pp.844~857 (2012)
  6. Yan Y, "Novel nomograms to predict lymph node metastasis and liver metastasis in patients with early colon carcinoma", J. Transl. Med, 17, pp.193~ (2019)
  7. Tang Q, "HOTAIR: An oncogenic long non-coding RNA in human cancer", Cell. Physiol. Biochem, 47, pp.893~913 (2018)
  8. Kopp F, "Functional classification and experimental dissection of long noncoding RNAs", Cell, 172, pp.393~407 (2018)
  9. Peng WX, "LncRNA-mediated regulation of cell signaling in cancer", Oncogene, 36, pp.5661~5667 (2017)
  10. Bhan A, "Long noncoding RNA and cancer: A new paradigm", Cancer Res, 77, pp.3965~3981 (2017)
  11. Ma Y, "Membrane-lipid associated lncRNA: A new regulator in cancer signaling", Cancer Lett, 419, pp.27~29 (2018)
  12. Li Q, "LINC01232 exerts oncogenic activities in pancreatic adenocarcinoma via regulation of TM9SF2", Cell Death Dis, 10, pp.698~ (2019)
  13. Meng LD, "Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK", ERK signaling pathway, 2020, pp.494, 107~120
  14. Chen L, "LncRNA, miRNA and lncRNA-miRNA interaction in viral infection", Virus Res, 257, pp.25~32 (2018)
  15. Huang Y, "The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases", J. Cell. Mol. Med, 22, pp.5768~5775 (2018)
  16. Zhao M, "Long intergenic non-coding RNA LINC01232 contributes to esophageal squamous cell carcinoma progression by sequestering microRNA-654-3p and consequently promoting hepatoma-derived growth factor expression", Int. J. Mol. Med, 46, pp.2007~2018 (2020)
  17. Shang A, "Long non-coding RNA CCAT1 promotes colorectal cancer progression by regulating miR-181a-5p expression", Aging, 12, pp.8301~8320 (2020)
  18. Qi X, "Biomarker discovery for the carcinogenic heterogeneity between colon and rectal cancers based on lncRNA-associated ceRNA network analysis", Front. Oncol, 10, pp.535985~ (2020)
  19. Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method", Methods (San Diego, Calif.), 25, pp.402~408 (2001)
  20. Chen S, "Long noncoding RNAs: functions and mechanisms in colon cancer", Mol. Cancer, 19, pp.167~ (2020)
  21. Mizerska-Kowalska M, "Neutral endopeptidase (NEP) is differentially involved in biological activities and cell signaling of colon cancer cell lines derived from various stages of tumor development", Tumour Biol, 37, pp.13355~13368 (2016)
  22. Rokavec M, "Cellular model of colon cancer progression reveals signatures of mRNAs, miRNA, lncRNAs, and epigenetic modifications associated with metastasis", Cancer Res, 77, pp.1854~1867 (2017)
  23. Wang SY, "Butyrate suppresses abnormal proliferation in colonic epithelial cells under diabetic state by targeting HMGB1", J. Pharmacol. Sci, 139, pp.266~274 (2019)
  24. Hong B, "Targeting tumor suppressor p53 for cancer therapy: strategies, challenges and opportunities", Curr. Drug Targets, 15, pp.80~89 (2014)
  25. Wang XW, "p53 tumor-suppressor gene: clues to molecular carcinogenesis", J. Cell. Physiol, 173, pp.247~255 (1997)
  26. Brachtendorf S, "Chemosensitivity of human colon cancer cells is influenced by a p53-dependent enhancement of ceramide synthase 5 and induction of autophagy", Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1863, pp.1214~1227 (2018)
  27. Moriichi K, "Autofluorescence imaging reflects the nuclear enlargement of tumor cells as well as the cell proliferation ability and aberrant status of the p53, Ki-67, and p16 genes in colon neoplasms", Molecules, 24, pp.1106~ (2019)
  28. Valentini A, "Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells", Cancer Biol. Ther, 6, pp.185~191 (2007)
  29. Wei Y, "Estrogen Receptor Beta (ERβ) mediated-cyclinD1 degradation via autophagy plays an antiproliferation role in colon cells", Int. J. Biol. Sci, 15, pp.942~952 (2019)
  30. Thompson EB, "The many roles of c-Myc in apoptosis", Ann. Rev. Physiol, 60, pp.575~600 (1998)
  31. Ebrahim AS, "Hematologic malignancies: newer strategies to counter the BCL-2 protein", J. Cancer Res. Clin. Oncol, 142, pp.2013~2022 (2016)
  32. Ramjiawan RR, "Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?", Angiogenesis, 20, pp.185~204 (2017)
  33. Apte RS, "VEGF in signaling and disease: Beyond discovery and development", Cell, 176, pp.1248~1264 (2019)
  34. Jiang Z, "Allostery in BAX protein activation", J. Biomol. Struct. Dyn, 34, pp.2469~2480 (2016)
  35. Matsumoto K, "Roles of VEGF-A signalling in development, regeneration, and tumours", J. Biochem, 156, pp.1~10 (2014)
  36. Lamouille S, "Molecular mechanisms of epithelial-mesenchymal transition", Nat. Rev. Mol. Cell Biol, 15, pp.178~196 (2014)
  37. Dongre A, "New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer", Nat. Rev. Mol. Cell Biol, 20, pp.69~84 (2019)
  38. Zeng M, "miR-378 suppresses the proliferation, migration and invasion of colon cancer cells by inhibiting SDAD1", Cell. Mol. Biol. Lett, 22, pp.12~ (2017)

관련 논문AI추천

Upregulated Long Noncoding RNA LINC01234 Predicts Unfavorable Prognosis for Colorectal Cancer and Negatively Correlates With KLF6 ExpressionFengsheng Zhou, Jun Chen, Pengxi Wu, Qiaoying Zhu, Xiao Jiang대한진단검사의학회 · Annals of Laboratory Medicine2020 · 제40권 제2호The Long Noncoding RNA DUXAP8 Facilitates the Malignant Progression of Colon Cancer via the microRNA-378a-3p/FOXQ1 AxisJin Jianqin, Shang Rui, Wang Yuecheng거트앤리버 소화기연관학회협의회 · Gut and Liver2025 · 제19권 제2호LINC00174 Facilitates Proliferation and Migration of Colorectal Cancer Cells via MiR-3127-5p/ E2F7 AxisLi Xiaofei, Li Yuzhen, Ma Yuhong, Tang Ning, Tang Yuanyuan, Wang Dengke한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2021 · 제31권 제8호Long Noncoding RNA HEIH Promotes Colorectal Cancer Tumorigenesis via Counteracting miR-939Mediated Transcriptional Repression of Bcl-xLChunhui Cui, Duanyang Zhai, Jinlong Yu, Lang Xie, Lianxu Cai, Qiaobin Duan대한암학회 · Cancer Research and Treatment2018 · 제50권 제3호Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200aFei Chen, Xiao-Fang Bai, Zheng-Bin Zhao연세대학교의과대학 · Yonsei Medical Journal2019 · 제60권 제8호Long Noncoding RNA N-BLR Upregulates the Migration and Invasion of Gastric Adenocarcinoma윤정호, Chan Hyuk Park, Hyo Joo Byun, Sang Kil Lee, Young Hoon Youn거트앤리버 소화기연관학회협의회 · Gut and Liver2019 · 제13권 제4호

이 간행물의 다른 논문 (14건)