LIM homeobox 6 (LHX6) has been reported to be downregulated and inhibits cell proliferation in various
cancers. Alternative splicing of LHX6 leads to six annotated
isoforms, which can be found in the NCBI database. However, the expression patterns and potential roles of these
isoforms remain poorly characterized in
cervical cancer. Here, we demonstrated that the LHX6
isoforms containing exon 12 (LHX6EX(+12) group) and
isoforms lacking exon 12 (LHX6EX(-12) group) were differentially expressed in cervical tissue by qRT-PCR. The
mRNA expression level of LHX6EX(+12) group was higher than that of LHX6EX(-12) group in
cervical cancer tissue. Knockdown of LHX6EX(+12) group and all LHX6
isoforms (LHX6All group) inhibited cell growth, increased cell apoptosis, and induced cell cycle arrest from G0/G1 phase to S phase in vitro. Consistently, overexpression of the LHX6EX(+12) group promoted
cervical cancer cell proliferation in vitro. In contrast, no significant differences in cell proliferation were found between LHX6EX(-12)
isoform knockdown group and its control.
RNA-sequencing suggested that the LHX6EX(+12)
isoform group might exert its
cancer-promoting effects in
cervical cancer via regulating MAPK signaling pathway. Downregulation of the LHX6EX(+12) group significantly suppressed the phosphorylation of MRK, ERK, JNK, and P38 at the
protein level. We also identified some unique biological processes and signaling pathways in which each
isoform group might be involved. In summary, our results indicated that LHX6EX(+12)
isoform group was the dominant oncogenic type of LHX6 in
cervical cancer, which may be a new
biomarker and a potential precise therapeutic target for
cervical cancer in the future.