Silencing of lncRNA LINC00346 Inhibits the Proliferation and Promotes the Apoptosis of Colorectal Cancer Cells Through Inhibiting JAK1/STAT3 Signaling

Abstract

Purpose: The study was aimed to investigate the effect and mechanism of lncRNA LINC00346 on cell proliferation and apoptosis of colorectal cancer (CRC).

Methods: The expression of lncRNA LINC00346 in CRC tissues and cells was detected by qRT-PCR. LINC00346 was overexpressed and silenced in HT29 and LoVo cells by the transfection of pcDNA-LINC00346 and si-LINC00346. The proliferation of CRC cells was detected by CCK-8 and colony-formation assay. The apoptosis was detected by flow cytometry assay. The expression of apoptosis-associated proteins (Caspase-3, Bcl-2, Bax) and JAK1/STAT3 signaling-associated proteins (JAK1, STAT3, p-JAK1, p-STAT3) was detected by Western blot. The tumor growth was detected in mice subcutaneous injected with transfected HT29 cells.

Results: LINC00346 was significantly upregulated in CRC tissues and cells. Overexpression of LINC00346 significantly increased the OD₄₅₀ values, number of colonies, decreased the apoptosis rate, upregulated Bcl-2, and downregulated Caspase-3 and Bax in HT29 and LoVo cells. Knockdown of LINC00346 exerted opposite results of proliferation and apoptosis on HT29 and LoVo cells. The expression levels of JAK1/JAK1 and p-STAT3/STAT3 were upregulated by LINC00346 overexpression. Tofacitinib (JAK1 inhibitor) reversed the tumor-promoting effect of LINC00346 overexpression on CRC cells. In vivo experiments further validated that LINC00346 overexpression promoted the growth of CRC xenograft tumors.

Conclusion: LncRNA LINC00346 promoted the proliferation and inhibited the apoptosis of CRC cells through activating JAK1/STAT3 signaling.

Keywords: JAK1/STAT3; LncRNA LINC00346; apoptosis; colorectal cancer; proliferation.