title: The long noncoding RNA HOXA transcript at the distal tip promotes colorectal cancer growth partially via silencing of p21 expression.
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.
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Lian
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Departments of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Taixing People's Hospital, Taixing, 225400, Jiangsu, People's Republic of China.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Peng
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Jirong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China. kemingwang@njmu.edu.cn.
authors.forename: Keming
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C000613830:long noncoding RNA HOTTIP, human
keywords: Cell proliferation; Colorectal cancer; HOTTIP; lncRNA; p21