Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 10;26(3):353-361.
doi: 10.3727/096504017X15002869385155. Epub 2017 Jul 26.

Long Noncoding RNA HOTAIR: An Oncogene in Human Cervical Cancer Interacting With MicroRNA-17-5p

Fei Ji  1 , Delinaer Wuerkenbieke  1 , Yan He  1 , Yan Ding  1 , Rong Du  1
Affiliations

Long Noncoding RNA HOTAIR: An Oncogene in Human Cervical Cancer Interacting With MicroRNA-17-5p

Fei Ji et al. Oncol Res. .

Abstract

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are a class of significant regulators in various tumorigenesis processes. The lncRNA homeobox transcript antisense RNA (HOTAIR) has been reported to act as a functional lncRNA in cervical cancer development. The present study investigated the underlying mechanism of HOTAIR and miR-17-5p in cervical cancer tumorigenesis. The results showed that HOTAIR expression was significantly upregulated in both cervical cancer tissues and cell lines. Loss-of-function experiments showed that HOTAIR knockdown inhibited the proliferation, migration, and invasion of cervical cells. In addition, miR-17-5p expression was downregulated in cervical cancer tissues and cell lines. Pearson's correlation analysis indicated that miR-17-5p expression was negatively correlated to that of HOTAIR. Luciferase reporter assay revealed that miR-17-5p directly targeted HOTAIR 3'-UTR. Rescue experiments showed that miR-17-5p knockdown could reverse the tumor-suppressing effect caused by si-HOTAIR transfection. In summary, our results reveal the tumor-promoting role of HOTAIR in cervical cancer via sponging miR-17-5p, providing a novel therapeutic target for future treatment of cervical cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Homeobox transcript antisense RNA (HOTAIR) was overexpressed in cervical cancer tissues and cell lines. (A) The expression level of HOTAIR was significantly higher in cervical cancer tissues than in normal tissues. (B) The expression level of HOTAIR was significantly higher in cervical cancer cell lines than in human keratinocyte cells. Data are presented as mean ± standard deviation (SD). **p < 0.01, ***p < 0.001, calculated with Student’s t-test.
Figure 2
Figure 2
Low expression of HOTAIR inhibited proliferation, migration, and invasion of cervical cancer cells. (A) The expression level of HOTAIR is significantly lower in HOTAIR siRNA-transfected cells than in controls. (B, C) CCK-8 assay results indicated that proliferation of cervical cancer cells was significantly decreased in a time-dependent manner after downregulation of HOTAIR. (D) The migration ability of cervical cancer cells was significantly suppressed after downregulation of HOTAIR. Random fields are shown. (E) The invasion ability of cervical cancer cells was significantly suppressed after downregulation of HOTAIR. Random fields are shown. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, calculated with Student’s t-test.
Figure 3
Figure 3
miR-17-5p expression is downregulated in cervical cancer tissues and cell lines. (A) miRNA expression profiles in cervical cancer tissue were determined by miRNA microarray. (B) The expression of miR-17-5p was significantly lower in cervical cancer tissues than in normal tissues. (C) The expression level of miR-17-5p was significantly lower in cervical cancer cell lines than in noncancer cells. Data are presented as mean ± SD. **p < 0.01, calculated with Student’s t-test.
Figure 4
Figure 4
HOTAIR regulated miR-17-5p expression via direct binding. (A) Pearson’s correlation analysis showed that the expression of miR-17-5p is negatively related to the expression of HOTAIR (R 2 = 0.182). (B) A presumptive complementary region between HOTAIR and miR-17-5p. (C) The dual-luciferase reporter assay indicated that there was certain possibility of 3′-UTR of HOTAIR (WT) and miR-17-5p sharing a complementary binding sequence (firefly luciferase activity in overexpressed miR-17-5p Caski cells was decreased by 63% compared to NC-transfected Caski cells). Data are presented as mean ± SD. **p < 0.01, calculated with Student’s t-test.
Figure 5
Figure 5
Functions of HOTAIR and miR-17-5p on cervical cancer Caski cells. (A) Expression of miR-17-5p in cervical cancer Caski cells after transfections. (B) Cell viability of cervical cancer Caski cells determined by the CCK-8 assay. (C, D) The cell migration and invasion abilities of cervical cancer Caski cells were determined by Transwell assays. Data are presented as mean ± SD. *p < 0.05, **p < 0.01 and #p < 0.05, ##p < 0.01, calculated with Student’s t-test.
See this image and copyright information in PMC

References

    1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D, Forman D, Bray F. GLOBOCAN 2012, cancer incidence and mortality worldwide. Int J Cancer 2013;65(7):56–67. - PubMed
    1. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132(5):1133–45. - PubMed
    1. Zhao FH, Lewkowitz AK, Hu SY, Chen F, Li LY, Zhang QM, Wu RF, Li CQ, Wei LH, Xu AD. Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: A pooled analysis of 17 population-based studies. Int J Cancer 2012;131(12):2929–38. - PMC - PubMed
    1. Kumar V, Westra HJ, Karjalainen J, Zhernakova DV, Esko T, Hrdlickova B, Almeida R, Zhernakova A, Reinmaa E, Vosa U, Hofker MH, Fehrmann RS, Fu J, Withoff S, Metspalu A, Franke L, Wijmenga C. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet. 2013;9(1):3201–13. - PMC - PubMed
    1. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR. Landscape of transcription in human cells. Nature 2012;489(7414):101–8. - PMC - PubMed