Role of LINC00332 in colorectal cancer progression and paclitaxel resistance

Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer deaths. Standard therapeutic management is faced with challenges like treatment resistance and late-stage diagnosis, highlighting a need for better diagnosis. LncRNAs are crucial in CRC progression and may serve as non-invasive biomarkers. For the first time, this study explores LINC00332 potential as a therapeutic and diagnostic marker in CRC.

Eighty fresh normal and tumor tissues were enrolled to evaluate the levels of LINC00332 expression using Real-time PCR method. LINC00332 ectopic expression was also done to evaluate its role in drug resistance and cell migration in HCT116 cells.

Ectopic expression of LINC00332 significantly induced NOTCH and WNT pathways in HCT116 cells. LINC00332 promoted EMT process through up regulation of Vimentin, CDH2, Snail, ZEB2, Slug, MMP10, and MMP3 while down regulation of CDH1 and OCLUDIN in HCT116 cells. LINC00332 significantly induced the HCT116 cell migration and paclitaxel (PTX) resistance in HCT116 cells (p < 0.0001). There was significant up regulation of LINC00332 in CRC clinical samples compared to normal margins (p = 0.042). There was significant up regulation of LINC00332 in stage I/II tumors that was located in transverse and left colon in comparison to right colon (p = 0.03). Tumors with perineural invasion had significant LINC00332 up regulation compared with negative ones in CRC patients (p = 0.02).

LINC00332 promotes PTX resistance and EMT in CRC via WNT and NOTCH pathways activation. It can also be suggested as a potential diagnostic marker in early-stage CRC patients. Targeting LINC00332 may enhance PTX response, warranting further studies for therapeutic application.