HOXC11 positively regulates the long non-coding RNA HOTAIR and is associated with poor prognosis in colon adenocarcinoma

Gong,Nana; Li,Fei; Wang,Yanan; Li,Zizi; Wang,Wanqiu; Gong,Tingting; Meng,Xiaojun; Chen,Hongtao

doi:10.3892/etm.2021.10745

HOXC11 positively regulates the long non-coding RNA HOTAIR and is associated with poor prognosis in colon adenocarcinoma

Authors:
- Nana Gong
- Fei Li
- Yanan Wang
- Zizi Li
- Wanqiu Wang
- Tingting Gong
- Xiaojun Meng
- Hongtao Chen
View Affiliations

Affiliations: Department of Laboratory Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, P.R. China, Department of Pharmacy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, P.R. China, Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, P.R. China, Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, P.R. China, Department of Endocrinology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong 519000, P.R. China
Published online on: September 16, 2021 https://doi.org/10.3892/etm.2021.10745
Article Number: 1310
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Colorectal cancer ranks third in terms of incidence and second in terms of mortality worldwide. The homeobox transcript antisense intergenic RNA (HOTAIR), which was found to be located on the antisense chain of the homeobox C (HOXC) gene cluster, is a long non‑coding RNA involved in multiple types of tumors. The role of HOXC11 in tumors remains unclear. Reverse transcription‑quantitative PCR was performed to detect the expression level of HOXC11 in colon adenocarcinoma. Cell proliferation and invasion were assessed. RNase protection assay was used to test the possibility of RNA duplex formation. The increased expression and co‑expression trend of HOXC11 and HOTAIR were identified in multiple types of cancer from The Cancer Genome Atlas and the results were validated in 12 colon adenocarcinoma and paired non‑tumor tissue samples. The expression of HOXC11 and HOTAIR was found to be associated with poor prognosis in colon adenocarcinoma and kidney renal clear cell carcinoma. Furthermore, HOXC11 was found to positively regulate HOTAIR by RNA duplex formation and promoted the proliferation and invasion of colon adenocarcinoma cells.

View Figures

View References

1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar
2	Williams C, DiLeo A, Niv Y and Gustafsson JA: Estrogen receptor beta as target for colorectal cancer prevention. Cancer Lett. 372:48–56. 2016.PubMed/NCBI View Article : Google Scholar
3	Batista PJ and Chang HY: Long noncoding RNAs: Cellular address codes in development and disease. Cell. 152:1298–1307. 2013.PubMed/NCBI View Article : Google Scholar
4	He Y, Meng XM, Huang C, Wu BM, Zhang L, Lv XW and Li J: Long noncoding RNAs: Novel insights into hepatocelluar carcinoma. Cancer Lett. 344:20–27. 2014.PubMed/NCBI View Article : Google Scholar
5	Fatica A and Bozzoni I: Long non-coding RNAs: New players in cell differentiation and development. Nat Rev Genet. 15:7–21. 2014.PubMed/NCBI View Article : Google Scholar
6	Kalwa M, Hänzelmann S, Otto S, Kuo CC, Franzen J, Joussen S, Fernandez-Rebollo E, Rath B, Koch C, Hofmann A, et al: The lncRNA HOTAIR impacts on mesenchymal stem cells via triple helix formation. Nucleic Acids Res. 44:10631–10643. 2016.PubMed/NCBI View Article : Google Scholar
7	Hong Q, Li O, Zheng W, Xiao WZ, Zhang L, Wu D, Cai GY, He JC and Chen XM: LncRNA HOTAIR regulates HIF-1α/AXL signaling through inhibition of miR-217 in renal cell carcinoma. Cell Death Dis. 8(e2772)2017.PubMed/NCBI View Article : Google Scholar
8	Fu WM, Zhu X, Wang WM, Lu YF, Hu BG, Wang H, Liang WC, Wang SS, Ko CH, Waye MM, et al: Hotair mediates hepatocarcinogenesis through suppressing miRNA-218 expression and activating P14 and P16 signaling. J Hepatol. 63:886–895. 2015.PubMed/NCBI View Article : Google Scholar
9	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010.PubMed/NCBI View Article : Google Scholar
10	Zhang A, Zhao JC, Kim J, Fong KW, Yang YA, Chakravarti D, Mo YY and Yu J: LncRNA HOTAIR enhances the androgen-receptor-mediated transcriptional program and drives castration-resistant prostate cancer. Cell Rep. 13:209–221. 2015.PubMed/NCBI View Article : Google Scholar
11	Heubach J, Monsior J, Deenen R, Niegisch G, Szarvas T, Niedworok C, Schulz WA and Hoffmann MJ: The long noncoding RNA HOTAIR has tissue and cell type-dependent effects on HOX gene expression and phenotype of urothelial cancer cells. Mol Cancer. 14(108)2015.PubMed/NCBI View Article : Google Scholar
12	Nnamani MC, Ganguly S, Erkenbrack EM, Lynch VJ, Mizoue LS, Tong Y, Darling HL, Fuxreiter M, Meiler J and Wagner GP: A derived allosteric switch underlies the evolution of conditional cooperativity between HOXA11 and FOXO1. Cell Rep. 15:2097–2108. 2016.PubMed/NCBI View Article : Google Scholar
13	Roumengous S, Rousset R and Noselli S: Polycomb and Hox genes control JNK-induced remodeling of the segment boundary during Drosophila morphogenesis. Cell Rep. 19:60–71. 2017.PubMed/NCBI View Article : Google Scholar
14	Kherdjemil Y, Lalonde RL, Sheth R, Dumouchel A, de Martino G, Pineault KM, Wellik DM, Stadler HS, Akimenko MA and Kmita M: Evolution of Hoxa11 regulation in vertebrates is linked to the pentadactyl state. Nature. 539:89–92. 2016.PubMed/NCBI View Article : Google Scholar
15	Zanatta A, Rocha AM, Carvalho FM, Pereira RM, Taylor HS, Motta EL, Baracat EC and Serafini PC: The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: A review. J Assist Reprod Genet. 27:701–710. 2010.PubMed/NCBI View Article : Google Scholar
16	Amândio AR, Necsulea A, Joye E, Mascrez B and Duboule D: hotair is dispensible for mouse development. PLoS Genet. 12(e1006232)2016.PubMed/NCBI View Article : Google Scholar
17	Chandrashekar DS, Bashel B, Balasubramanya SA, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BV and Varambally S: UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 19:649–658. 2017.PubMed/NCBI View Article : Google Scholar
18	Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM and Haussler D: The human genome browser at UCSC. Genome Res. 12:996–1006. 2002.PubMed/NCBI View Article : Google Scholar
19	Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St Laurent G III, Kenny PJ and Wahlestedt C: Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 14:723–730. 2008.PubMed/NCBI View Article : Google Scholar
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
21	Ali A, Creevey L, Hao Y, McCartan D, O'Gaora P, Hill A, Young L and McIlroy M: Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer. Breast Cancer Res. 17(123)2015.PubMed/NCBI View Article : Google Scholar
22	Loewen G, Jayawickramarajah J, Zhuo Y and Shan B: Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol. 7(90)2014.PubMed/NCBI View Article : Google Scholar
23	Bhatlekar S, Fields JZ and Boman BM: HOX genes and their role in the development of human cancers. J Mol Med (Berl). 92:811–823. 2014.PubMed/NCBI View Article : Google Scholar
24	Bhatlekar S, Fields JZ and Boman BM: Role of HOX genes in stem cell differentiation and cancer. Stem Cells Int. 2018(3569493)2018.PubMed/NCBI View Article : Google Scholar
25	Du H and Taylor HS: The role of Hox genes in female reproductive tract development, adult function, and fertility. Cold Spring Harb Perspect Med. 6(a023002)2015.PubMed/NCBI View Article : Google Scholar
26	Luo Z, Rhie SK, Lay FD and Farnham PJ: A Prostate cancer risk element functions as a repressive loop that regulates HOXA13. Cell Rep. 21:1411–1417. 2017.PubMed/NCBI View Article : Google Scholar
27	Zhu H, Dai W, Li J, Xiang L, Wu X, Tang W, Chen Y, Yang Q, Liu M, Xiao Y, et al: HOXD9 promotes the growth, invasion and metastasis of gastric cancer cells by transcriptional activation of RUFY3. J Exp Clin Cancer Res. 38(412)2019.PubMed/NCBI View Article : Google Scholar
28	Luo H, Wang F, Zha J, Li H, Yan B, Du Q, Yang F, Sobh A, Vulpe C, Drusbosky L, et al: CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia. Blood. 132:837–848. 2018.PubMed/NCBI View Article : Google Scholar
29	Taketani T, Taki T, Shibuya N, Kikuchi A, Hanada R and Hayashi Y: Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13). Cancer Res. 62:4571–4574. 2002.PubMed/NCBI
30	Gu BW, Wang Q, Wang JM, Xue YQ, Fang J, Wong KF, Chen B, Shi ZZ, Shi JY, Bai XT, et al: Major form of NUP98/HOXC11 fusion in adult AML with t(11;12)(p15;q13) translocation exhibits aberrant trans-regulatory activity. Leukemia. 17:1858–1864. 2003.PubMed/NCBI View Article : Google Scholar
31	Mitchelmore C, Troelsen JT, Sjöström H and Norén O: The HOXC11 homeodomain protein interacts with the lactase-phlorizin hydrolase promoter and stimulates HNF1alpha-dependent transcription. J Biol Chem. 273:13297–13306. 1998.PubMed/NCBI View Article : Google Scholar
32	Zhang Y and Cao X: Long noncoding RNAs in innate immunity. Cell Mol Immunol. 13:138–147. 2016.PubMed/NCBI View Article : Google Scholar
33	Idda ML, Munk R, Abdelmohsen K and Gorospe M: Noncoding RNAs in Alzheimer's disease. Wiley Interdiscip Rev RNA. 9(9)2018.PubMed/NCBI View Article : Google Scholar
34	Wang W, He X, Zheng Z, Ma X, Hu X, Wu D and Wang M: Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma. Mol Cancer. 16(75)2017.PubMed/NCBI View Article : Google Scholar
35	Özeş AR, Miller DF, Özeş ON, Fang F, Liu Y, Matei D, Huang T and Nephew KP: NF-κB-HOTAIR axis links DNA damage response, chemoresistance and cellular senescence in ovarian cancer. Oncogene. 35:5350–5361. 2016.PubMed/NCBI View Article : Google Scholar
36	Xue X, Yang YA, Zhang A, Fong KW, Kim J, Song B, Li S, Zhao JC and Yu J: LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 35:2746–2755. 2016.PubMed/NCBI View Article : Google Scholar
37	Woo CJ and Kingston RE: HOTAIR lifts noncoding RNAs to new levels. Cell. 129:1257–1259. 2007.PubMed/NCBI View Article : Google Scholar