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Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression

View Article: PubMed Central - PubMed

ABSTRACT

Spleen tyrosine kinase (SYK) has been reported as a potential tumor suppressor in colorectal cancer (CRC). However, the role of alternative splicing of SYK in carcinogenesis remains unclear. In the present study, SYK isoforms were overexpressed in the human CRC HCT 116 cell line using lentiviral expression vectors to investigate the biological functions of full length SYK [SYK(L)] and short form SYK [SYK(S)] in CRC. Real-time cellular analysis and the 5-ethynyl-2-deoxyuridine assay were used to detect the effects of SYK(L) and SYK(S) on cell proliferation. Cell cycle progression and migration were assessed via flow cytometry and Transwell assays, respectively. The results revealed that the recombinant lentivirus with SYK(L) overexpression significantly suppressed the proliferation and metastasis of CRC cells, while SYK(S) overexpression did not. In addition, MTS assays demonstrated that SYK(L) and SYK(S) increased the cellular sensitivity to 5-fluorouracil (5-FU), suggesting that SYK(L) and 5-FU produce a significant synergistic effect on CRC cell proliferation, while SYK(S) has an effect on modulating CRC 5-FU sensitivity. Furthermore, quantitative polymerase chain reaction results revealed that SYK(L) was downregulated in 69% of 26 pairs of CRC and adjacent non-cancerous tissues, whereas SYK(S) exhibited no significant differences between tumor and normal tissues. Overall, the present data provides evidence that SYK(L) is a tumor suppressor in CRC, and both SYK(L) and SYK(S) may serve as important predictors in the chemotherapeutic treatment of CRC.

No MeSH data available.


Expression of SYK isoforms in CRC tissues. SYK(L) and SYK(S) mRNA expression was detected by quantitative polymerase chain reaction in 26 pairs of CRC tissues and matched adjacent non-cancerous tissues. Glyceraldehyde 3-phosphate dehydrogenase was used as an endogenous control. SYK, spleen tyrosine kinase; SYK(L), SYK full length; SYK(S), SYK short form.
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f4-ol-0-0-4858: Expression of SYK isoforms in CRC tissues. SYK(L) and SYK(S) mRNA expression was detected by quantitative polymerase chain reaction in 26 pairs of CRC tissues and matched adjacent non-cancerous tissues. Glyceraldehyde 3-phosphate dehydrogenase was used as an endogenous control. SYK, spleen tyrosine kinase; SYK(L), SYK full length; SYK(S), SYK short form.

Mentions: To investigate the expression pattern of SYK splice isoforms SYK(L) and SYK(S) in CRC patients, the mRNA levels of SYK(L) and SYK(S) were assessed in 26 tumor tissues and paired normal tissues using qPCR. As shown in Fig. 4, the levels of SYK(L) were significantly lower in tumor tissues compared with normal tissues (P=0.049). However, the levels of SYK(S) had no significant differences between tumor tissues and normal tissues (P=0.403). Therefore, SYK(L) may be recognized as a potential tumor suppressor in CRC.


Alternative splicing of spleen tyrosine kinase differentially regulates colorectal cancer progression
Expression of SYK isoforms in CRC tissues. SYK(L) and SYK(S) mRNA expression was detected by quantitative polymerase chain reaction in 26 pairs of CRC tissues and matched adjacent non-cancerous tissues. Glyceraldehyde 3-phosphate dehydrogenase was used as an endogenous control. SYK, spleen tyrosine kinase; SYK(L), SYK full length; SYK(S), SYK short form.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998349&req=5

f4-ol-0-0-4858: Expression of SYK isoforms in CRC tissues. SYK(L) and SYK(S) mRNA expression was detected by quantitative polymerase chain reaction in 26 pairs of CRC tissues and matched adjacent non-cancerous tissues. Glyceraldehyde 3-phosphate dehydrogenase was used as an endogenous control. SYK, spleen tyrosine kinase; SYK(L), SYK full length; SYK(S), SYK short form.
Mentions: To investigate the expression pattern of SYK splice isoforms SYK(L) and SYK(S) in CRC patients, the mRNA levels of SYK(L) and SYK(S) were assessed in 26 tumor tissues and paired normal tissues using qPCR. As shown in Fig. 4, the levels of SYK(L) were significantly lower in tumor tissues compared with normal tissues (P=0.049). However, the levels of SYK(S) had no significant differences between tumor tissues and normal tissues (P=0.403). Therefore, SYK(L) may be recognized as a potential tumor suppressor in CRC.

View Article: PubMed Central - PubMed

ABSTRACT

Spleen tyrosine kinase (SYK) has been reported as a potential tumor suppressor in colorectal cancer (CRC). However, the role of alternative splicing of SYK in carcinogenesis remains unclear. In the present study, SYK isoforms were overexpressed in the human CRC HCT 116 cell line using lentiviral expression vectors to investigate the biological functions of full length SYK [SYK(L)] and short form SYK [SYK(S)] in CRC. Real-time cellular analysis and the 5-ethynyl-2-deoxyuridine assay were used to detect the effects of SYK(L) and SYK(S) on cell proliferation. Cell cycle progression and migration were assessed via flow cytometry and Transwell assays, respectively. The results revealed that the recombinant lentivirus with SYK(L) overexpression significantly suppressed the proliferation and metastasis of CRC cells, while SYK(S) overexpression did not. In addition, MTS assays demonstrated that SYK(L) and SYK(S) increased the cellular sensitivity to 5-fluorouracil (5-FU), suggesting that SYK(L) and 5-FU produce a significant synergistic effect on CRC cell proliferation, while SYK(S) has an effect on modulating CRC 5-FU sensitivity. Furthermore, quantitative polymerase chain reaction results revealed that SYK(L) was downregulated in 69% of 26 pairs of CRC and adjacent non-cancerous tissues, whereas SYK(S) exhibited no significant differences between tumor and normal tissues. Overall, the present data provides evidence that SYK(L) is a tumor suppressor in CRC, and both SYK(L) and SYK(S) may serve as important predictors in the chemotherapeutic treatment of CRC.

No MeSH data available.