RETRACTED ARTICLE: Repressing phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma by microRNA-142-3p restrains the progression of hepatocellular carcinoma

Abstract

This paper probes the mechanisms underlying miR-142-3p’s modulation of hepatocellular carcinoma (HCC) invasion and apoptosis. Quantitative real-time PCR and Western blot monitored the miR-142-3p profile in HCC tissues and non-tumor tissues. The correlation between miR-142-3p expression and HCC patients’ clinicopathological indicators was analyzed. miR-142-3p overexpression and knockdown models were established in HCC cell lines. Cell proliferation was gauged by the colony formation assay and BrdU staining. For measuring apoptosis, flow cytometry and Western blot were implemented. Transwell assay tested cell migration and invasion. miR-142-3p mimics or inhibitors were transfected in Huh7 and HCCLM3 cells. The targeting association between miR-142-3p and PIK3CG was predicted through bioinformatics and further verified by related experiments. The influence of PIK3CG overexpression on miR-142-3p’s role in HCC was assayed. A xenografted tumor model was built in mice to validate miR-142-3p knockdown’s influence on HCC in vivo . As a result, miR-142-3p exhibited a decreased profile in HCC tissues and cells. Overexpressing miR-142-3p accelerated apoptosis and suppressed the PI3K/AKT/HIF-1α signal. Knocking down miR-142-3p presented opposite effects. PIK3CG overexpression dampened the anti-tumor effect of miR-142-3p. miR-142-3p repressed HCC invasion and intensified apoptosis to restrain HCC by abating the PIK3CG-mediated PI3K/AKT/HIF-1α pathway.

Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches

“…This target belongs to the family of transcription factors that regulate gene expression, morphogenesis and cellular differentiation. This work, together with those of Zeng et al [49] and Cui et al [64], points towards the relevance of miR-142-3p in downregulating HCC.…”

“…All the works presented in this section are summarized in Table 2. As reported (see Section 4.1: miRNAs and siRNAs and 4.3: circRNAs), miR-142-3p has gained attention in the HCC field [49,63]. Cui et al [64] showed that lncRNA lnc712 sponges miR-142-3p.…”

“…Its level is increased in prostate cancer and its targeting reduces cancer cell growth. Thus, the data of Zeng et al [49] further point toward the importance of increasing the level of miR-142-3p in HCC.…”

“…Moreover, lncRNA712 can target the miR-142-3p/Bach-1 pathway, promoting HCC development (see also Section 4.2: lncRNAs) [64]. Zeng et al [49] further studied the role of miR-142-3p in HCC, confirming that its levels are reduced in HCC and that patients with higher expression levels have longer survival. In cultured HCC cell lines (Huh7 and HCCLM3), miR-142-3p transfection reduced the proliferation rate and promoted cell apoptosis.…”

“…Notably, knockdown of circWHSC1 diminished HCC cell proliferation and metastasis in vitro and downregulated tumorigenesis in vivo. From the mechanistic point of view, the authors showed that circWHSC1 acts as a sponge for miR-142-3p, a relevant miRNA in HCC (Zeng et al [49]). In turn, a reduction in miR-142-3p levels increased the amount of one of its targets, i.e., homeobox A1 (HOXA1).…”