Tumor suppressor LHX6 upregulation contributes to the inhibitory effect of miR‐346 knockdown on colorectal cancer cell growth

• Published in: Environmental toxicology 2022-03, Vol.37 (3), p.435-445
• Main Authors: Li, Xianzhe, Zhou, Yeqi, Wen, Penghao, Yuan, Yan, Xiao, Zhenghong, Shi, Hengwei, Zhou, Hailang
• Format: Article
• Language: English
• Subjects: AKT protein; Akt/mTOR pathway; Apoptosis; Assaying; Cancer; Cell growth; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cells; Cholecystokinin; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Evaluation; Gene Expression Regulation, Neoplastic; Genes; growth; Homeobox; Humans; Inactivation; Kinases; LHX6; LIM-Homeodomain Proteins - genetics; MicroRNAs - genetics; miR‐346; Neoplasms; Nerve Tissue Proteins - genetics; Nucleotide sequence; PCR; Proliferation; Rapamycin; TOR protein; Transcription Factors - genetics; Tumor suppressor genes; Tumors; Up-Regulation
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23410

Colorectal cancer (CRC) is one of the prevalent types of human malignancies and ranks as the second leading cause of cancer‐associated death worldwide. Dysregulated miRNAs have been promulgated as oncogenes or tumor‐suppressive genes participating in the initiation and progression of CRC. A recent study reported that miR‐346 was highly expressed in CRC patients. However, the biological role and underlying mechanism of miR‐346 in CRC remain elusive. qRT‐PCR and western blot assays were employed to detect miR‐346 and LIM homeobox domain 6 (LHX6) expression in CRC cells. Cell proliferation was evaluated by CCK‐8 and BrdU assays. Apoptosis was evaluated by TUNEL assay. The interaction between miR‐346 and LHX6 was assessed by luciferase reporter assay. Results showed that miR‐346 expression was increased and LHX6 expression was reduced in CRC cells. miR‐346 knockdown and LHX6 overexpression inhibited proliferation and promoted apoptosis of CRC cells. Additionally, we found that miR‐346 negatively regulated LHX6 expression in CRC cells by directly targeting LHX6. LHX6 knockdown partially attenuated anti‐miR‐346‐induced proliferation reduction and apoptosis promotion in CRC cells. Furthermore, miR‐346 knockdown inhibited the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in CRC cells by targeting LHX6. The present study indicated that miR‐346 knockdown repressed cell growth in CRC cells by upregulating LHX6, and this was associated with inactivation of the Akt/mTOR pathway.