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Tumor Biology

, Volume 37, Issue 6, pp 7431–7440 | Cite as

The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression

  • Yifan Lian
  • Jie Ding
  • Zhihong Zhang
  • Yongguo Shi
  • Ya Zhu
  • Juan Li
  • Peng Peng
  • Jirong Wang
  • Yingrui Fan
  • Wei De
  • Keming Wang
Original Article

Abstract

Accumulating evidence strongly suggests that dysregulation of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. However, the biological role of HOTTIP in colorectal cancer (CRC) has not yet been discussed. Here, we report that HOTTIP acts as a functional oncogene in the pathogenesis of CRC. In this study, quantitative polymerase chain reaction (qPCR) was performed to detect the expression of HOTTIP in 48 pairs of colorectal cancer samples. We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. Collectively, our results suggest that HOTTIP is involved in the progression of CRC and may provide evidence for HOTTIP being a target for therapy of this disease.

Keywords

Colorectal cancer HOTTIP p21 Cell proliferation lncRNA 

Notes

Acknowledgments

This work was supported by the Medical Science and Technology Development Foundation, the Jiangsu Province Department of Health (H201407), the Six Talents Peak Project of Jiangsu province (WSN-050), and the Natural Science Foundation of Jiangsu Province of China (BK20151578).

Compliance with ethical standards

Informed consent was obtained from all patients. Our study was approved by the Research Ethics Committee of Nanjing Medical University, China.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yifan Lian
    • 1
  • Jie Ding
    • 1
  • Zhihong Zhang
    • 2
  • Yongguo Shi
    • 3
  • Ya Zhu
    • 1
  • Juan Li
    • 1
  • Peng Peng
    • 1
  • Jirong Wang
    • 1
  • Yingrui Fan
    • 1
  • Wei De
    • 4
  • Keming Wang
    • 1
  1. 1.Department of Oncology, Second Affiliated HospitalNanjing Medical UniversityNanjingChina
  2. 2.Departments of PathologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  3. 3.Department of OncologyTaixing People’s HospitalTaixingChina
  4. 4.Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingChina

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