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Expression and function of transmembrane 4 superfamily proteins in digestive system cancers
Wensheng Qiu
Affiliated Hospital of Medical College Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5063-7830
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied.
Methods We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo.
Results Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30 . TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis.
Conclusions Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.
Keywords
transmembrane 4 superfamily, digestive system cancers, bioinformatics analysis, proliferation, metastasis
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Due to technical limitations Tables 1-3 are available as downloads in the Supplementary Files.
Table 1. Significant changes of TSPANs expression in transcription level between HCC and normal liver tissues (ONCOMINE).
HCC: hepatocellular carcinoma
Table 2. Significant changes of TSPANs expression in transcription level between CRC and normal colorectal tissues (ONCOMINE).
CRC: colorectal cancer
Table 3. Significant changes of TSPANs expression in transcription level between GC and normal gastric tissues (ONCOMINE).
GC: gastric cancer
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On 24 Mar, 2020
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Reviewer #7 agreed
On 19 Mar, 2020
Reviewer #6 agreed
On 17 Mar, 2020
Reviewer #3 agreed
On 16 Mar, 2020
Reviewer #4 agreed
On 16 Mar, 2020
Reviewer #5 agreed
On 16 Mar, 2020
Reviewer #2 agreed
On 15 Mar, 2020
Reviewers invited
Invitations sent on 14 Mar, 2020
Reviewer #1 agreed
On 14 Mar, 2020
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On 13 Mar, 2020
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This preprint is under consideration at Cancer Cell International. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
Expression and function of transmembrane 4 superfamily proteins in digestive system cancers
Wensheng Qiu
Affiliated Hospital of Medical College Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5063-7830
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 15 Jun, 2020
Published
On 16 Jul, 2020
No community comments so far
Editorial decision: Accept
On 14 Jun, 2020
Editor assigned
On 09 Jun, 2020
Submission checks complete
On 08 Jun, 2020
Editor invited
On 08 Jun, 2020
No comments provided
Editorial decision: Major revision
On 02 Apr, 2020
Review #5 received
Received 01 Apr, 2020
Review #4 received
Received 31 Mar, 2020
Review #7 received
Received 30 Mar, 2020
Review #3 received
Received 27 Mar, 2020
Reviewer #8 agreed
On 24 Mar, 2020
Review #1 received
Received 22 Mar, 2020
Review #2 received
Received 22 Mar, 2020
Reviewer #7 agreed
On 19 Mar, 2020
Reviewer #6 agreed
On 17 Mar, 2020
Reviewer #3 agreed
On 16 Mar, 2020
Reviewer #4 agreed
On 16 Mar, 2020
Reviewer #5 agreed
On 16 Mar, 2020
Reviewer #2 agreed
On 15 Mar, 2020
Reviewers invited
Invitations sent on 14 Mar, 2020
Reviewer #1 agreed
On 14 Mar, 2020
Editor assigned
On 13 Mar, 2020
Editor invited
On 12 Mar, 2020
Submission checks complete
On 07 Mar, 2020
First submitted
On 06 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Cancer Cell International.
Background Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied.
Methods We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo.
Results Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30 . TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis.
Conclusions Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Due to technical limitations Tables 1-3 are available as downloads in the Supplementary Files.
Table 1. Significant changes of TSPANs expression in transcription level between HCC and normal liver tissues (ONCOMINE).
HCC: hepatocellular carcinoma
Table 2. Significant changes of TSPANs expression in transcription level between CRC and normal colorectal tissues (ONCOMINE).
CRC: colorectal cancer
Table 3. Significant changes of TSPANs expression in transcription level between GC and normal gastric tissues (ONCOMINE).
GC: gastric cancer