eP650 - The Effect of Overexpression of Regenerating Islet-derived type4 Isoform 2 on Colon Cancer Cell Proliferation

Monday, June 3, 2024

2:03 PM – 2:08 PM ET, USA

Location: Baltimore Convention Center, Room 318-320

ePoster Presenter(s)

Aya Kobari, MD

Undergraduate
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
Juntendo University Faculty of Medicine
Tokyo, Tokyo, Japan

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

Yuki Ii, MD

Undergraduate
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine
Tokyo, Tokyo, Japan

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
Takahiro Irie, MD

Undergraduate
Department of Coloproctlogical Surgery, Juntendo University Faculty of Medicine
Juntendo University
Suginami-ku, Tokyo, Japan

All relevant financial disclosures have been managed and will be listed below.
This individual has no financial relationships with ineligible companies.
Kiichi Sugimoto, MD

Associate Professor
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
Juntendo University Faculty of Medicine
2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
HK

Hiroshi Koide, Ph.D.

Professor
Laboratory of Molecular and Biochemical Research, Biomedical Research Core Facilities, Juntendo University
Bunkyo-ku, Tokyo, Japan

Disclosure information not submitted.

Senior Author(s)

KS

Kazuhiro Sakamoto, M.D.Ph.D.

Professor
Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo
2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan

Disclosure information not submitted.

Purpose/Background: Regenerating islet-derived type4 (REG4) is highly expressed in various cancers, such as pancreatic cancer, gastric cancer, ovarian cancer, and colon cancer. It also increases cancer cell proliferation and inhibits apoptosis. In colorectal cancer, some reports have shown that REG4 contributes to resistance to chemotherapy and radiotherapy, and a high REG4 expression is associated with a poor prognosis. In humans, REG4 has two isoforms translated from three RNA splicing variants. However, previous studies on REG4 have mostly focused on isoform 1, with none examining the function of isoform 2. We investigated the effect of REG4 isoform 2 on colon cancer cell proliferation.Methods/Interventions: We compared the expression of REG4 in non-carcinoma-derived cells and carcinoma-derived cells for the two isoforms using real-time quantitative polymerase chain reaction. In addition, the same comparison was made between normal and cancer tissues collected from colon resection specimens in colorectal cancer surgery cases in our department. To examine whether or not the signaling pathways of the two isoforms were the same, the expression of sox2, Klf4, Bclxl, and Blc2, which are involved in REG4 isoform 1 signaling, was examined in REG4 isoform 2-overexpressing HCT116 cells. To examine the effect of REG4 isoform 2 on colon cancer cell proliferation, we performed a soft agar colony formation assay. In addition, we injected REG4 isoform 2-overexpressing HCT116 cells subcutaneously into NOD/SCID mice to compare tumor volumes.Results/Outcomes: Similar to isoform 1, the expression of REG4 isoform 2 was enhanced in colon cancer cell-derived cell lines compared to normal tissue-derived cell lines. The expression of REG4 isoform 2 in colon cancer tissues was higher than that in normal tissues at almost the same frequency as that of REG4 isoform 1. The expression of sox2, Klf4, Bclxl, and Blc2 in REG4 isoform 2-overexpressing HCT116 cells was not enhanced compared to the control cells. Compared to the control group, REG4 isoform 2-overexpressing HCT116 cells proliferated significantly in the soft agar colony formation assay (p=0.036). The assay using NOD/SCID mice showed no significant difference in tumor volume; however, tumors tended to be larger in the REG4 isoform 2-overexpressing group than in the control group (p=0.063).Conclusion/

Discussion: REG4 isoform 2 demonstrated the potential to promote colon cancer cell proliferation. Therefore, inhibition of REG4 isoform 2 is expected to be a promising treatment strategy in colorectal cancer.