Colon cancer-associated transcript-1 enhances glucose metabolism and colon cancer cell activity in a high-glucose environment in vitro and in vivo

Abstract

Background: Our study aims to investigate the effect of colon cancer-associated transcript-1 (CCAT-1) on colon cancer cells' activity and metabolism under different glucose environments in vitro and in vivo. Methods: The levels of proliferation, migration, glucose, lactic acid, glucose metabolism-related enzymes, apoptosis genes, epithelial-mesenchymal transition (EMT) marker proteins, and PI3K/Akt/C-MYC pathway in CCAT-1-silenced SW620 cells cultured with different glucose levels were tested. Twenty BALB/C nude mice with hyperglycemia or normal blood sugar were transplanted with CCAT-1-silenced SW620 cells, blood glucose levels, lactic acid, insulin, and volume of transplanted tumor cells, the expression of EMT marker proteins, and PI3K/Akt/C-MYC pathway was detected. Results: The levels of proliferation, migration, glucose, lactic acid, LDH-A, PKM2, and HK2 decreased, apoptosis increased in SW620 cells cultured with low glucose or silenced CCAT-1 (P<0.05); levels of E-cadherin and ZO-1 significantly increased, and levels of N-cadherin, vimentin, and p-Akt decreased in CCAT-1-silenced SW620 cells cultured with high glucose (P<0.05). Hyperglycemic nude mice transplanted with CCAT-1-silenced colon cancer cells showed decreased tumor volume, blood glucose, lactic acid, insulin, P-AKT, and P-C-MYC than EV group (P<0.05). Conclusions: CCAT-1 can enhance glucose metabolism and proliferation and migration of colon cancer cells by upregulating the expression of glycolysis enzymes, inhibiting apoptosis, activating the Akt/C-MYC pathway, and promoting EMT expression.

LncRNA ANRIL promotes glucose metabolism and proliferation of colon cancer in a high-glucose environment and associated with worse outcome in diabetic colon cancer patients

“…Studies in cancer cells show that hyperglycemia promotes cancer cell proliferation by oncogene or metabolic and molecular changes [25]. A recent study found that colon cancer cells cultivated with high glucose had better proliferation ability than colon cancer cells cultured with low glucose [47].…”

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer

“…Thus, how CCAT 1 facilitates tumorigenesis in CRC? Current studies suggest that CCAT 1 induces CRC cell proliferation through upregulating oncoproteins c-MYC and oncogenic mRNA tumor suppressor candidate 3 (TUSC3), the target of miR-181b-5p in CRC cells ( 24 , 49 ); enhances glucose metabolism to provide energy supply for the growth of colon cancer cells ( 78 ); facilitates CRC cell migration and invasion through accelerating EMT process and negatively modulate miR-218 as well as hsa-miR-4679 ( 67 , 69 ), and lastly inhibits colon cancer cell apoptosis by sponging miR-181a-5p ( Table 2 ) ( 47 ).…”

“…By sponging miR-181b-5p in CRC cells, CCAT 1 positively regulates the expression of TUSC3 which in turn promote proliferation, migration, invasion, and accelerates tumor growth ( 49 ). CCAT 1 upregulates the glycolytic pathway in colon cancer cells by increasing the expression levels of glycolysis rate-limiting enzymes in colon cancer cells and promoting lactic acid production ( 78 ). This action provides energy supply for the proliferation of colon cancer cells as malignant tumors primarily rely on the glycolytic pathway for energy supply ( 78 ).…”

“…CCAT 1 upregulates the glycolytic pathway in colon cancer cells by increasing the expression levels of glycolysis rate-limiting enzymes in colon cancer cells and promoting lactic acid production ( 78 ). This action provides energy supply for the proliferation of colon cancer cells as malignant tumors primarily rely on the glycolytic pathway for energy supply ( 78 ). Cui et al also show that high glucose levels or hyperglycemia enhance the oncogenic effect of CCAT 1 on colon cancer cell proliferation, anti-apoptotic and migration ( 78 ).…”

“…This action provides energy supply for the proliferation of colon cancer cells as malignant tumors primarily rely on the glycolytic pathway for energy supply ( 78 ). Cui et al also show that high glucose levels or hyperglycemia enhance the oncogenic effect of CCAT 1 on colon cancer cell proliferation, anti-apoptotic and migration ( 78 ).…”