Downregulation of hnRNP K by RNAi inhibits growth of human lung carcinoma cells

Tang,Fengming; Li,Weimin; Chen,Yan; Wang,Dongmei; Han,Juan; Liu,Dan

doi:10.3892/ol.2014.1832

2014-April Volume 7 Issue 4

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

2014-April Volume 7 Issue 4

Full Size Image

Article

Downregulation of hnRNP K by RNAi inhibits growth of human lung carcinoma cells

Authors:
- Fengming Tang
- Weimin Li
- Yan Chen
- Dongmei Wang
- Juan Han
- Dan Liu
View Affiliations / Copyright

Affiliations: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
Pages: 1073-1077
|
Published online on: January 28, 2014

https://doi.org/10.3892/ol.2014.1832
Expand metrics +

Abstract

Lung cancer is one of the most common malignancies worldwide, but its pathogenesis remains unknown. The current study examined the effects of heterogeneous nuclear ribonucleoprotein K (hnRNP K)‑targeted small interfering RNA (siRNA) on the growth and apoptosis of lung cancer cells in vitro. The expression of hnRNP K was studied by the SP method of immunohistochemistry in lung tissue samples of 70 cases of lung cancer. hnRNP K siRNA were transfected into human lung cancer cell line, A549, using Lipofectamine 2000. Cells transfected with siRNAn and untreated served as controls. The inhibitory effect of siRNA on the expression of hnRNP K mRNA and protein was detected by reverse transcription polymerase chain reaction and western blot analysis. The change in cell cycling and cell apoptosis of siRNA‑treated cells was detected by flow cytometry. The rates of positive hnRNP K expression in lung tumors of diameters ≤3, 3‑5 and ≥5 cm, were 38.5, 95.2 and 91.7%, respectively. A significant difference was identified between lung tumors with diameters of ≤3 and ≥3 cm (P<0.01). The expression of hnRNP K mRNA was significantly inhibited in siRNA‑transfected cells compared with that in control cells (P<0.05). Notably, hnRNP K protein decreased in hnRNP K siRNA‑transfected cells, but exhibited no effect on the control groups. siRNA targeting human hnRNP K effectively inhibited the growth of lung cancer cell line, A549, and the distribution of the cell cycle. The apoptosis rate was 4.79% and the number of cells increased in the G0/G1 phase from 37.21 to 85.60% and decreased in the S and G2/M phases from 47.71 to 13.50% and 14.00 to 0.32%, respectively, following 24 h of transfection. hnRNP K siRNA promotes A549 apoptosis and the apoptosis rate was 4.79% (P<0.01). Therefore, hnRNP K siRNA may inhibit the proliferation of A549 cells. In addition, hnRNP K promotes the growth of lung cancer cells and, therefore, hnRNP K siRNA may inhibit the growth and increase the apoptosis of lung cancer cells.

View Figures

View References

1	Krecic AM and Swanson MS: hnRNP complexes: composition, structure, and function. Curr Opin Cell Biol. 11:363–371. 1999. View Article : Google Scholar : PubMed/NCBI
2	Dreyfuss G, Matunis GM, Piñol-Roma S and Burd CG: hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem. 62:289–321. 1993. View Article : Google Scholar : PubMed/NCBI
3	Swanson MS: Functions of nuclear pre-mRNA/mRNA binding proteins. Pre-mRNA Processing. Lamond AL: Springer-Verlag GmbH; Berlin: pp. 17–33. 1995, View Article : Google Scholar
4	Nigg EA: Nucleocytoplasmic transport: signals, mechanisms and regulation. Nature. 386:779–787. 1997. View Article : Google Scholar : PubMed/NCBI
5	Nakielny S and Dreyfuss G: Nuclear export of proteins and RNAs. Curr Opin Cell Biol. 9:420–429. 1997. View Article : Google Scholar : PubMed/NCBI
6	Piñol-Roma S and Dreyfuss G: Transcription-dependent and transcription independent nuclear transport of hnRNP proteins. Science. 253:312–314. 1991.PubMed/NCBI
7	Piñol-Roma S and Dreyfuss G: Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 355:730–732. 1992.PubMed/NCBI
8	Carson JH, Kwon S and Barbarese E: RNA trafficking in myelinating cells. Curr Opin Neurobiol. 8:607–612. 1998. View Article : Google Scholar
9	Carpenter B, Mackay C, Alnabulsi A, et al: The roles of heterogeneous nuclear ribonucleoproteins in tumour development and progression. Biochim Biophys Acta. 1765:85–100. 2006.PubMed/NCBI
10	Bomsztyk K, Denisenko O and Ostrowski J: hnRNP K: one protein multiple processes. Bioessays. 26:629–638. 2004. View Article : Google Scholar : PubMed/NCBI
11	Bomsztyk K, Van Seuningen I, Suzuki H, et al: Diverse molecular interactions of the hnRNP K protein. FEBS Lett. 403:113–115. 1997. View Article : Google Scholar : PubMed/NCBI
12	Michelotti EF, Michelotti GA, Aronsohn AI and Levens D: Heterogeneous nuclear ribonucleoprotein K is a transcription factor. Mol Cell Biol. 16:2350–2360. 1996.
13	Kühn H, Heydeck D, Brinckman R and Trebus F: Regulation of cellular 15-lipoxygenase activity on pretranslational, translational, and posttranslational levels. Lipids. 34(Suppl): S273–S279. 1999.PubMed/NCBI
14	Mandal M, Vadlamudi R, Nguyen D, et al: Growth factors regulate heterogeneous nuclear ribonucleoprotein K expression and function. J Biol Chem. 276:9699–9704. 2001. View Article : Google Scholar : PubMed/NCBI
15	Kawamura K, Sato N, Fukuda J, et al: Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos. Dev Biol. 256:331–341. 2003. View Article : Google Scholar : PubMed/NCBI
16	Ostrowski J and Bomsztyk K: Nuclear shift of hnRNP K protein in neoplasms and other states of enhanced cell proliferation. Br J Cancer. 89:1493–1501. 2003. View Article : Google Scholar : PubMed/NCBI
17	Yano M, Okano HJ and Okano H: Involvement of Hu and heterogeneous nuclear ribonucleoprotein K in neuronal differentiation through p21 mRNA post-transcriptional regulation. J Biol Chem. 280:12690–12699. 2005. View Article : Google Scholar : PubMed/NCBI
18	Iyer VR, Eisen MB, Ross DT, et al: The transcriptional program in the response of human fibroblasts to serum. Science. 283:83–87. 1999. View Article : Google Scholar : PubMed/NCBI
19	Adolph D, Flach N, Mueller K, et al: Deciphering the cross talk between hnRNP K and c-Src: the c-Src activation domain in hnRNP K is distinct from a second interaction site. Mol Cell Biol. 27:1758–1770. 2007. View Article : Google Scholar
20	Bartek J and Lukas J: Pathways governing G1/S transition and their response to DNA damage. FEBS Lett. 490:117–122. 2001. View Article : Google Scholar : PubMed/NCBI
21	Taylor WR and Stark GR: Regulation of the G2/M transition by p53. Oncogene. 20:1803–1815. 2001. View Article : Google Scholar : PubMed/NCBI
22	Moumen A, Masterson P, O’Connor MJ and Jackson SP: hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell. 123:1065–1078. 2005. View Article : Google Scholar : PubMed/NCBI
23	Laury-Kleintop LD, Tresini M and Hammond O: Compartmentalization of hnRNP-K during cell cycle progression and its interaction with calponin in the cytoplasm. Cell Biochem. 95:1042–1056. 2005. View Article : Google Scholar : PubMed/NCBI
24	Harris SL and Levine AJ: The p53 pathway: positive and negative feedback loops. Oncogene. 24:2899–2908. 2005. View Article : Google Scholar : PubMed/NCBI
25	Waga S, Hannon GJ, Beach D and Stillman B: The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature. 369:574–578. 1994. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Downregulation of hnRNP K by RNAi inhibits growth of human lung carcinoma cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Related Articles